Due to the complexity of biological transformations, developing model-based strategies to optimize and control bioprocesses is nontrivial. Hybrid models combining a mechanistic description of known influential factors with machine learning to infer the missing influential factors from data have been reported as powerful tools for bioprocesses applications. The artificial neural network is one of the most popular machine learning methods in this case. This paper presents a systematic literature review by computerized search across two databases: Scopus and Web of Science, and backward citation. The PRISMA method was applied to selecting the publications and 159 research articles were categorized as hybrid model applications to bioprocesses problems. It was found that hybrid models were mainly applied in upstream operation steps with a predominance of bioreaction steps. In downstream processing, chromatography appeared as a more recent research topic, with a relatively small number of publications. Furthermore, holistic hybrid modeling applications that integrate data and knowledge from several bioprocess steps will likely emerge in the future, enabling better optimization and control of the bioprocess’s platform. The combination of other machine learning methods with the hybrid neural network model is another opportunity that could improve the output of the model.

ReviewInter-Specific Hybridization in Cotton (Gossypium hirsutum ) for Crop ImprovementMuhammad Zafar Iqbal 1, * Muhammad Anwar2

Hazard is a term associated with a substance that is likely to cause an injury in a given environment or situation. Industrial hazards are major occupational health and safety (OHS) issue in Pharmaceutical manufacturing. In recent years chemical safety and the sound management of chemicals have seen great progress at the global level. At the same time, the rapid growth in production and dissemination of both natural and synthetic chemicals has led to concern about their impact on the natural environment, and human health. In this way, the pharmaceutical industry has come to occupy a unique position. Practically no other commercial enterprises present such as a wide variety of potentially toxic exposures or such a rapidly changing advent of new chemical substances. In the pharmaceutical industry, this dynamic situation has been created by the increasing application of organic chemical synthesis as a technique for producing therapeutic substances. This renders the work of the plant physician so instructive. Industrial safety is needed to check all the possible chances of accidents for preventing loss of life and permanent disability of any industrial worker, any damage to machine and material leads to the loss of the whole establishment.

Data integrity is an important current issue for regulators around the world. During inspections a multitude of problems being found by the pharmaceutical regulatory agency because poor practices develop the substandard product for patients. Collection of various types of information and results collectively made in the form of data. This data becomes one of the most valuable assets of any organization but without integrity, this data is not much useful. Accuracy and original data increase the chances of stability and performance of an organization.

Recently it has been growing interest in investing solid state transition forms prepared by different technique. The majority of drugs are administered in solids form. Among all newly discovered chemical entities about 40% drugs are lipophillic and fail to reach market due to their poor aqueous solubility. Problem of solubility is a major challenge for formulation scientist, which can be resolved by different technological approaches. Simvastatin belong to class of antihyperlipidemic drugs having very low solubility and falls in category II Class of BCS. Polymorphism and solid state transitions change the solid-state property which is significantly influence the performance of the final product such as solubility, Melting Point, Dissolution Rate and flow property. Optimization process like RCM and CCD design was used to study the effect of variables such as solubility and melting point for quality determination of formulation. Solvent evaporation method is used in this study to prepare new transition form. This technique has more advantages and it is preferred method over others such as spray drying, sonication and homogenization. Through the characterized analysis (SEM, XRD, ATR, DSC, Solublity and melting point) of optimised form, given reliably confirmation data that the new solid state transition forms is amorphous form. It is more soluble than crystalline form.

Samples taken from pond water (Padila), river ganga water (Sangam, Allahabad) sewage water (Yamuna drainage) supply water from Municipal Corporation (Daraganj) were found that Ganga water (Sangam) has positive (large, small, medium) plaque formation other pond water, sewage water, supply water from municipal Corporation do not have plaque formation. It can be predict that Ganga water has high presence of S. aureus plaque formation for bacteriophages. Help in therapeutic process, drug target discovery, bacteriophages isolate from environment or Ganga water sample to specifically target pathogenic bacteria and eliminate them from foods. Bacteriophages approved or use in food safety application, genetically engineered phages to specifically target bacterial virulence-associated genes, control multidrug resistant S. aureus, implications in biofilm treatment, the progress in the knowledge about phage genomics, immunobiology and experimental therapy in animals and in humans suggest that phages could become the antibacterial drugs of the 21st century.

Isaac Newton, Philosophiæ Naturalis Principia retypeset via LaTeX by Project Gutenberg

The Human Monkeypox virus belongs to the Poxvirdiae family of the Orthopoxvirus genus. This virus is seen to get transmitted to humans predominantly by contact transmission via infected animals and humans. It exhibits a range of clinical features apart from the common rash, swollen lymph nodes, and flu-like symptoms.

Neurinomas are tumors of Schwann cells of the peripheral nerve sheath. Sacral location is rarely reported especially in spondyloarthritis patients. Herein, we report a case of uncommon pygalgia in a 25-year-old man with history of a non-radiographic axial spondyloarthritis and in whom the diagnosis of sacral neurinoma was established.

Anterior cervical spine surgery with placement of osteosynthesis material is common in cervical trauma. The following is the case of a 52-year-old with progressive dysphagia and endoscopic examination incidentally evidenced a plate anterior metal in the posterior aspect of the hypopharynx.

JOURNAL: BJOGDATE 08_25_2022TITLE: Mini commentary on “Familial aggregation of stillbirth: a pedigree analysis of a matched case control study” BJOG_22-0217Author: Matthew A. Shear, MDa,bAuthor Affiliations:a Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Franciscob Division of Medical Genetics, Department of Pediatrics, University of California, San FranciscoDespite advances in genomics, the underlying cause of many stillbirths remains elusive. The emotional toll that a stillbirth takes on families, as well as the providers caring for them, is hard to overstate. Karyotype may identify a causative aneuploidy or large unbalanced translocation, but only in about 6% of stillbirths. Chromosomal microarray is higher yield, but still only identifies pathogenic copy number variants in about 10% of stillbirth cases (Reddy et al. N Engl J Med. 2012). The addition of exome sequencing to microarray only yielded a plausible genetic explanation in 15 out of 246 cases, or about 6% (Stanley et al. N Engl J Med. 2020). This suggested that non-mendelian mechanisms may play a significant role in stillbirth (Wojcik et al N. Engl J Med. 2020), although single gene pathogenic variants are poorly understood at the fetal level relative to the postnatal setting. The non-genetic mechanisms underlying stillbirth are also poorly understood at present, including viral infections, environmental toxins, and comorbid conditions.Workalemahu and their colleagues present a unique analysis suggesting genomic heritability of stillbirth in some families. Using a robust matched case-control study of over 9000 stillbirths and 390 high-risk pedigrees from the Utah Population Database, they calculated the familial standardized incidence ratio and risk of stillbirth among first, second, and third-degree relatives of the pregnant individuals who had experienced stillbirth. In their adjusted model, among all relatives of an individual who experienced stillbirth, there was a relative risk of stillbirth of 1.1 (95% CI 1.00-1.22). This study adds further evidence there are heritable genetic etiologies of stillbirth not yet fully described.Many non-genetic contributors to stillbirth risk may also cluster in families. In the present study, when adjusting for maternal race/ethnicity, socioeconomic status, and education, the elevations in stillbirth risk became attenuated, although this may be due to collinearity among variables used in the model. Health behaviors are informed through regional and family culture, leading to patterns in diet, nutrition, and exercise. These patterns contribute to modifiable health conditions known to impact stillbirth risk, including hypertension, obesity, diabetes, and smoking status. We also know the incidence of stillbirth is higher in lower income versus higher income countries, higher among individuals of lower educational attainment versus higher education, and higher among African American and Black individuals compared to White, likely complicated by the impacts of systemic racism. This is to say nothing of the additional social determinants of health that may impact families across generations.As Workalemahu and colleagues note, there is still much unknown about complex outcomes such as stillbirth. Their findings support that for a patient with a high-risk pedigree, genomic testing may prove informative. Future epigenetic and functional studies may help understand variants at the tissue level, and the impact of comorbidities on gene expression. Together with fetal genome sequencing, previously unexplained cases of stillbirth might be solved, improving patient counseling, and possibly changing clinical management. While genomic testing offers promise to explain a subset of stillbirths, we should not neglect the “non-mendelian” and non-genetic factors that continue to play a significant role in stillbirth risk.

BJOG-22-0382.R1: Implementing Effective Investigations for Cause of StillbirthElizabeth M McClure, PhDRobert L Goldenberg, MDRTI International, Durham, NCColumbia University, New York, NYStillbirth is one of the most common adverse pregnancy outcomes in low and middle-income countries (LMICs), with rates in the range of 40 to 50 per thousand births in some regions [1]. International goals aim for no country to have a rate of >10 per thousand births by 2035 [Hug L, et al. Lancet. 2021;398(10302):772-85]. To achieve this, a better understanding of stillbirth causes often requiring additional investigations is critical. For several reasons, including low prioritization, inadequate resources, and hesitancy by families and providers, investigations on stillbirth causes in LMICs have been limited to date.Bedwell et al used a grounded theory approach to explore the views of women, partners, families, health workers and community leaders in Malawi, Tanzania, and Zambia regarding investigations to determine the cause(s) of stillbirth [Bedwell et al, BJOG (in press)]. While most would like more information regarding the stillbirth, the authors noted cultural and religious obstacles to performing the investigations, including preferences for quick burial, reluctance to disfigure the deceased fetus, concerns about blame, as well as costs.One test to inform cause of stillbirths is minimally invasive tissue sampling (MITS), using needle biopsies to obtain internal organ tissue for histological evaluation and microbial analyses. For a study on causes of stillbirth in Pakistan and India, we explored the acceptability of MITS among parents, relatives, religious leaders, and government officials [Feroz A, et al. Reprod Health.2019;16(1):53]. The perceived benefits included knowing the cause of death, and both personal and societal benefits in preventing subsequent stillbirths. Concerns regarded rapid burial and reluctance to disfigure the stillborn. In Pakistan, with some caveats, religious leaders approved, and, when MITS was undertaken, in both Pakistan and India, approximately 50% of the parents consented for the MITS procedure.Because obstacles to testing in general and to MITS specifically relate to time, cost, and disfigurement, we have considered which examinations feasible in LMICs provide the most information at minimal cost. Page et al., in a similar exercise in a US study, noted that the most useful test was placental histology (65%) followed by full autopsy (42%) [Page JM, Obstet Gynecol 2017;129(4):699-706.]. No other tests were useful for >12% of cases. Similar studies have rarely been performed in LMICs. The prevalence of the causes relates to the frequency of tests’ usefulness. In high-income countries where birth asphyxia and infection have been reduced, congenital and genetic anomalies have assumed a larger proportion of stillbirths, and testing for those conditions using karyotyping and other genetic tests become proportionately more important. However, in many LMICs, birth asphyxia remains the major cause of stillbirth and genetic issues play a smaller proportional role.To develop the most effective methodology to determine cause of stillbirth, the prevalent conditions, and the tests’ usefulness to diagnose those conditions should be considered together. Importantly, the community and other stakeholder’s perceived benefits and obstacles to various tests as described in the Bedwell, et al must be considered to ultimately be successful in implementing the necessary investigations.For LMICs, given that asphyxia and infection appear to be major causes of stillbirth, tests to diagnose these conditions will likely be important to implement, including the obstetric history and histological placental evaluation for diagnosing asphyxia and infection. Of potential information gained from MITS, histology of the fetal lung, and bacteriological assessment of the fetal blood and brain/CSF may be the most useful. Thus, by considering the prevalence of the causes of stillbirth, the usefulness of tests to diagnose the prevalent conditions, and importantly addressing the community’s sense of benefit and obstacles, an effective approach to stillbirth cause of death investigation can be developed.Declaration of Interest: The authors declare no conflicts of interest.

Aim: The effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with stage III chronic kidney disease (CKD) are still subject to debate. We therefore assessed and compared the effectiveness and safety of DOACs vs. warfarin in this population. Methods: A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed an oral anticoagulant (OAC) was created using administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs. warfarin initiation. Treatment groups were compared in an on-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. Results. A total of 8,899 included patients filled a new OAC claim: 3,335 for warfarin and 5,564 DOACs. Compared with warfarin, rivaroxaban 15 mg and 20 mg presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk (Hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.65–0.88) and a similar safety risk (HR 0.94; 95% CI 0.66–1.35), whereas apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95% CI 0.79–1.26) and a lower safety risk (HR 0.65; 95% CI 0.43–0.99). Conclusion: In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Surface modified iron-oxide based engineered nanomaterials for hyperthermia therapy of cancer cellsMehak1, Rajkumar P Thummer2, Lalit M. Pandey1*1Bio-interface & Environmental Engineering LabDepartment of Biosciences and Bioengineering,Indian Institute of Technology Guwahati, Assam, 781039, India2Laboratory for Stem Cell Engineering and Regenerative MedicineDepartment of Biosciences and Bioengineering,Indian Institute of Technology Guwahati, Assam, 781039, India* Corresponding author: Tel. +91-361-258-3201; Fax +91-361-258-2249Email addresses: mehak1998@iitg.ac.in, rthu@iitg.ac.in, lalitpandey@iitg.ac.in

Economic evaluations are increasing being conducted in the maternity setting, with many randomised controlled trials conducted with a health economic component. A key criticism of economic evaluation in maternity care is a lack of robust data collection and measurement, inconsistencies in methodology and lack of adherence to reporting guidelines. This article provides a guide to the design of economic evaluations alongside clinical trials in maternal health. We cover economic concepts and considerations for the maternity setting and provide examples from the United Kingdom and Australia. We seek to improve the quality, consistency, and transparency of economic evaluations in maternal health.

Purpose: This article attempts to deal with the events that took place during the advent (reappearance) of Imam Mahdi, the Savior of all the worlds. In fact, in this article, we will discuss the forces that will join him when the Imam of the time appears, and above all, with Imam Hussein and how globalization can pave the way for Imam Mahdi's world revolution. Also, this research was conducted to answer and clarify three questions that stated in the Introduction section. Methods: We performed our methods in 4 stages: Identifying studies, Selection of Studies, Collating Studies, Reporting results. Results: One of the reasons why the Imam of the Age (Imam Mahdi) rises is because of the killing of Imam Hussein, and God has made a firm promise that he will take revenge on any of the perpetrators who led this incident by Imam Mahdi. Imam Hussein also states that the basis of his rising was inviting people to the Quran and the Prophet's Sunnah. Conclusion: God helps Imam Mahdi and Jesus Christ to establish divine government on earth, and this is accepted by Muslims and Christians. Dread and terror, as part of Imam Mahdi's power, will move in advance of his soldiers. Imam Mahdi will appear with the aim of reforming humanity and spreading justice in the world. We hope this article will take an important step in acquainting people with Imam Mahdi and Jesus Christ and paving the ground for their reappearance.

A document by Reza Rezaie Khanghah. Click on the document to view its contents.

Purpose: In this article, we will discuss the narrations and prophecies that exist in Islam, both in Shia, Sunni and other religions regarding Imam Mahdi. This article also attempts to deal with Holy Fatima and her characteristics. Also, we will show that Imam Mahdi is mentioned not only in other religions but also in other books. Also, this research was conducted to answer and clarify three questions that stated in the Introduction section. Methods: We performed our methods in 4 stages: Identifying studies, Selection of Studies, Collating Studies, Reporting results. Results: According to Abrahamic religions, a person will reappear and establish fairness and justice with the help of God, who is called Imam Mahdi and based on the opinion of Christians, he is Christ. If the Shiites, may Allah help them in His obedience, had fulfilled their covenant with united hearts, then there would have been no delay in meeting the Promised Saviour. Conclusion: The concept of Imam Mahdi is universal and cannot just be rejected. The appearance of Imam Mahdi will coincide with the coming back of Jesus Christ. Imam Mahdi, with the assistance of the Messiah, will ensure the completion and practical actualization of the mission of the Prophet Muhammad. The Hidden Imam wrote to Abu-Omar Ameri: The Prophet’s daughter (Holy Fatima) is a nice model for me. We hope this article will take an important step in acquainting people with Imam Mahdi and Jesus Christ and paving the ground for their reappearance.

Purpose: This article covers the events and incidents predicted before and after the appearance of Imam Mahdi and Jesus Christ. This article seeks to address the facts and inform you about the system of government of Imam Mahdi and Jesus Christ. Also, miracles and the titles of Imam Mahdi are other topics that were mentioned in this article. Also, this research was conducted to answer and clarify three questions that stated in the Introduction section. Methods: We performed our methods in 4 stages: Identifying studies, Selection of Studies, Collating Studies, Reporting results. Results: Imam Mahdi's world government follows the pattern of the Prophet's method of rule in early Islam. Jesus Christ has a special status in the Quranic literature and in the hadith, and plays a special role in establishing the divine government with Imam Mahdi. Imam Mahdi's system of government is unlike any government the world has ever known. Conclusion: Among the issues that exist in the apocalypse, we are faced with an issue called Imam Mahdi. In fact, Imam Mahdi is the savior of Muslims and all people with Jesus Christ. Imam Mahdi will form a just government in the world like his ancestors. We hope this article will take an important step in acquainting people with Imam Mahdi and Jesus Christ and paving the ground for their reappearance.

Auriculocondylar syndrome (ARCND) is a genetic and rare craniofacial condition caused by abnormal development of the first and second pharyngeal arches during the embryonic stage and is characterized by peculiar auricular malformations (question mark ears), mandibular condyle hypoplasia, micrognathia and other less-frequent features. GNAI3, PLCB4 and EDN1 have been identified as pathogenic genes in this syndrome so far, all of which are implicated in the EDN1-EDNRA signal pathway. Therefore, ARCND is genetically classified as ARCND1, ARCND2 and ARCND3 based on the mutations in GNAI3, PLCB4 and EDN1, respectively. ARCND is inherited in an autosomal dominant or recessive mode with significant intra- and interfamilial phenotypic variation and incomplete penetrance, rendering its diagnosis difficult and therapies individualized. To raise clinicians’ awareness of the rare syndrome, we focused on the currently known pathogenesis, pathogenic genes, clinical manifestations and surgical therapies in this review.

Cooling tower is an important part of circulating cooling water system. This paper studies the counter-flow wet seawater shower cooling tower, establishes and verifies the detailed thermal performance calculation model. The influences of salinity, inlet velocity and droplet diameter on cooling efficiency, heat dissipation, gas-phase thermal efficiency and exergy efficiency were analyzed. The results showed that the cooling efficiency, exergy efficiency, gas-phase thermal efficiency and heat dissipation of the upper jet column were 15.59%, 4.89%, 8.62% and 34.58% higher than those of the lower jet column, respectively. With the increase of droplet diameter, decreased by 38.76%, Q decreased by 78.11%, decreased by 26.30% and decreased by 33.53% under standard salinity conditions. Under high salinity conditions, is reduced by 35.1%, is reduced by 17.16% and is reduced by 30.55%.With the increase of air velocity, increased by 13.76%, Q increased by 22.44%, decreased by 6.66%and decreased by less than 2% under the standard salt condition.Under high salinity conditions, compared with the standard salinity, the average reduction of is 2.96%, the average reduction of is 1.63% and the average reduction of is 2.73%. Through the optimization analysis of seawater cooling tower, it is obvious that selecting the best operating conditions can improve the heat and moisture exchange characteristics of seawater cooling tower.

科学合理布设耕地质量（CLQ）监测点，可以及时准确地提供耕地质量现状和变化信息，对保障国家粮食安全具有重要意义。传统的 CLQ 监测点选择方法是基于土地利用斑块的 CLQ。由于大补丁可能有不同等级，被选为监控点会降低监控CLQ的可靠性。此外，传统的监测点部署方法主要只考虑CLQ，而忽略了道路可达性和地形等因素，导致部分监测点无法进入。因此，为了提高 CLQ 监测的可靠性，本研究提出了一种部署 CLQ 监测点的新方法。第一的，像素尺度的 CLQ 是使用遗传算法 - 反向传播神经网络 (GA-BPNN) 模型基于具有 30 m 空间分辨率的 Landstat8 数据估计的。其次，采用分层抽样模型确定最佳样本点。最后，应用改进的空间模拟退火算法（ISSA），同时考虑坡度和道路可达性，以优化监测点的位置。本研究在中国广东省广州市从化区进行。结果突出表明 (1) 与测量的 CLQ 的准确度相比，准确度 (R 应用改进的空间模拟退火算法（ISSA），同时考虑坡度和道路可达性，以优化监测点的位置。本研究在中国广东省广州市从化区进行。结果突出表明 (1) 与测量的 CLQ 的准确度相比，准确度 (R 应用改进的空间模拟退火算法（ISSA），同时考虑坡度和道路可达性，以优化监测点的位置。本研究在中国广东省广州市从化区进行。结果突出表明 (1) 与测量的 CLQ 的准确度相比，准确度 (R2  =   0.63, RMSE = 79.32, NRMSE = 13.77%) 用遥感技术估计的 CLQ 是可靠的，不同等级的像素级 CLQ 数据比斑块级 CLQ 数据更合理。(2)基于分层抽样模型，最终在研究区确定了132个监测点。（3）与空间模拟退火算法（SSA）和标准网格法相比，本研究提出的方法总分更高（F=94.61）。此外，获得的样本点主要位于道路和平坦地形附近。这样可以有效避开人迹罕至的地方。因此，基于本研究提出的新方法的结果为获得最佳CLQ监测点提供了科学依据和技术支持。

Mucormycosis was an acute and invasive fungal infection with a high mortality rate. The treatment of mucormycosis was challenging. And the incidence of the mucormycosis seems to be increasing. The key to Mucormycosis therapy not only depend on anti-Mucor infection, but also included the management of some risk factors. Liposomal amphotericin B (L-AMB) was the first line drug to treat mucormycosis. The dosage regimen recommended by the guideline was often associated with higher nephrotoxicity and morbidity. A pharmacokinetic/pharmacodynamic (PKPD) model was conducted to evaluate suitable dosage regimens in Mucormycosis patients. 10mg/kg/day LAMB recommended in the guidelines might not be needed. 5mg/kg/day LAMB might be sufficient to achieve the target value of PKPD and indicated a good anti-Mucor effect. Successful management of mucormycosis was also based on suitable management of several risk factors which played a very important role in the progression of mucormycosis, such as iron factor, diabetes mellitus with acidosis and thrombosis. Application of deferasirox, statins and keep platelet level might be promising approaches in mucormycosis therapy.

Key points: (no abstract required) • Cochlear implant effectiveness in asymmetric hearing loss and single-sided deafness is well established, but rarely covered by health care systems. • Continuation of wearing the implant beyond the first year could be considered as an indirect indicator of subjective benefit. • Percentage of cochlear implant abandon at 5-years post-implantation was very low in patients with asymmetric hearing loss and single-sided deafness. • High education level, low audibility and good unaided speech perceptions scores of the contralateral acoustic-hearing ear were positive prognostic factors of CI use. • The low percentage of non-users is an additional strong argument to recommend cochlear implantation in patients with asymmetric hearing loss and single-sided deafness, on the ear with a profound hearing loss, especially in case of frail contralateral acoustic-hearing ear.