bluuebunny/crossref_metadata_2025 huggingface dataset:
Reinforcement learning evaluation of treatment policies for patients with hepatitis C virus
Authors: Oselio Brandon , Singal Amit G. , Zhang Xuefei , Van Tony , Liu Boang , Zhu Ji , Waljee Akbar K.
Published: March 2022

Background

Evaluation of new treatment policies is often costly and challenging in complex conditions, such as hepatitis C virus (HCV) treatment, or in limited-resource settings. We sought to identify hypothetical policies for HCV treatment that could best balance the prevention of cirrhosis while preserving resources (financial or otherwise).

Methods

The cohort consisted of 3792 HCV-infected patients without a history of cirrhosis or hepatocellular carcinoma at baseline from the national Veterans Health Administration from 2015 to 2019. To estimate the efficacy of hypothetical treatment policies, we utilized historical data and reinforcement learning to allow for greater flexibility when constructing new HCV treatment strategies. We tested and compared four new treatment policies: a simple stepwise policy based on Aspartate Aminotransferase to Platelet Ratio Index (APRI), a logistic regression based on APRI, a logistic regression on multiple longitudinal and demographic indicators that were prespecified for clinical significance, and a treatment policy based on a risk model developed for HCV infection.

Results

The risk-based hypothetical treatment policy achieved the lowest overall risk with a score of 0.016 (90% CI 0.016, 0.019) while treating the most high-risk (346.4 ± 1.4) and the fewest low-risk (361.0 ± 20.1) patients. Compared to hypothetical treatment policies that treated approximately the same number of patients (1843.7 vs. 1914.4 patients), the risk-based policy had more untreated time per patient (7968.4 vs. 7742.9 patient visits), signaling cost reduction for the healthcare system.

Conclusions

Off-policy evaluation strategies are useful to evaluate hypothetical treatment policies without implementation. If a quality risk model is available, risk-based treatment strategies can reduce overall risk and prioritize patients while reducing healthcare system costs.
Geo-analysis: the distribution of community health workers in relation to the HIV prevalence in KwaZulu-Natal province, South Africa
Authors: Khumalo G. E. , Ntuli S. , Lutge E. , Mashamba-Thompson T. P.
Published: March 2022

Background

The South African Ward Based Primary Health Care Outreach Team (WBPHCOT) policy framework states that the distribution of community health workers (CHWs) should be proportional to levels of poverty and disease within the population. We aimed to describe the spatial distribution of CHWs in relation to the prevalence of the Human Immunodeficiency Virus (HIV) which has itself been associated with poverty in previous studies.

Methods

This was a descriptive, cross-sectional study in which secondary data was used for geospatial analysis. Based on the extrapolation from the norm of one WBPHCOT per 6000 individuals, we utilized geographic information system (GIS) methods to visualize the distribution of CHWs in relation to the prevalence of HIV in KwaZulu-Natal (KZN). Dot density mapping was used to visualize the random distribution of CHWs in relation to HIV prevalence and population in the districts. The districts’ HIV prevalence, number of PLWH, ratio of CHW: people living with HIV (PLWH), ratio of CHW: population and poverty scores were mapped using choropleth mapping. MapInfo Pro 17.0 was used to map geospatial presentation of the data.

Results

Overall, KZN province showed under allocation of CHWs with a CHW: people ratio of 1: 1156 compared to the estimated norm of 1: 600–1000. At district level, only two of 11 districts met the suggested norm of CHW: PLWH (1: 109–181). This indicates shortages and misallocation of CHWs in the nine remaining districts. Furthermore, our findings showed extensive geospatial heterogeneity with no clear pattern in the distribution of CHWs. There was no relationship between CHW distribution and HIV prevalence or poverty scores in the districts.

Conclusion

This study shows inequality in the distribution of CHWs which may be associated with inequalities in the provision of HIV related services. It is critical to strengthen the response to the HIV epidemic through the appropriate distribution of CHWs especially in those districts with high levels of HIV prevalence and poverty.
The evolution of dam-litter microbial flora from birth to 60 days of age
Authors: Del Carro Angela , Corrò Michela , Bertero Alessia , Colitti Barbara , Banchi Penelope , Bertolotti Luigi , Rota Ada
Published: March 2022

Background

Early bacterial colonization in puppies is still a poorly understood phenomenon. Although the topic is of considerable interest, a big gap in knowledge still exists on the understanding of timing and features of neonatal gut colonization. Thence, the purpose of this study was to evaluate the relationship between dam and litter microbial flora, in vaginally delivered puppies, from birth to two months of age. Bacteria were identified using MALDI-TOF, an accurate and sensitive method, and cluster analysis of data provided a new insight on the investigated topic.

Methods

Six dam-litter units of two medium size breeds were enrolled in the study. Vaginal and colostrum/milk samples were collected from dams after delivery and 48h post-partum, while rectal samples were taken from dams and puppies after delivery and at day 2, 30 and 60 (T2, T30 and T60, respectively) post-partum. Bacterial isolation and identification were performed following standard techniques, then the data were analyzed using a new approach based on bacterial genus population composition obtained using a wide MALDI-TOF screening and cluster analysis.

Results

Forty-eight bacteriological samples were collected from the dams and 145 from their 42 puppies. Colostrum/milk samples (n = 12) showed a bacterial growth mainly limited to few colonies. Staphylococci, Enterococci, E. coli, Proteus spp. were most frequently isolated. All vaginal swabs (n = 12) resulted in bacteria isolation (medium to high growth). Streptococci, Enterococci, E. coli were the most frequently detected. E. coli, Proteus mirabilis, Enterococcus spp., Streptococcus spp. were often obtained from dams’ and puppies’ rectal swabs. Clostridia, not isolated in any other sampling site, were rarely found (n = 3) in meconium while they were more frequently isolated at later times (T2: n = 30; T30: n = 17; T60: n = 27).

Analysis of the bacterial genus pattern over time showed a statistically significant reduction (P < 0.01) in the heterogeneity of microbial composition in all time points if compared to birth for each dam-litter unit. These results were confirmed with cluster analysis and two-dimensional scaling.

Conclusion

This novel data analysis suggests a fundamental role of the individual dam in seeding and shaping the microbiome of the litter. Thus, modulating the dam’s microbiota may positively impact the puppy microbiota and benefit their health.
Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes for 20 families with familial exudative vitreoretinopathy
Authors: Dan Handong , Wang Dongdong , Huang Zixu , Shi Qianqian , Zheng Miao , Xiao Yuanyuan , Song Zongming
Published: March 2022

Background

Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR.

Methods

All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant.

Results

Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families.

Conclusions

These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.
Heterogeneous effects of COVID-19 control measures on tuberculosis in South Korea: an analysis of case notification data
Authors: Kim Honghyok , Kang Young Ae , Kim Hee-Jin , Choi Hongjo
Published: March 2022

Coronavirus disease (COVID-19) responses such as social distancing practices can decrease health care access and tuberculosis (TB) notification, particularly among individuals aged 60 years or older. Conversely, they can increase TB notification among younger individuals. These results may be attributable to household transmission and the similarity of TB respiratory symptoms to COVID-19.
Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss
Authors: Simeone Paola , Tripaldi Romina , Michelsen Annika , Ueland Thor , Liani Rossella , Ciotti Sonia , Birkeland Kåre I. , Gulseth Hanne L. , Di Castelnuovo Augusto , Cipollone Francesco , Aukrust Pål , Consoli Agostino , Halvorsen Bente , Santilli Francesca
Published: March 2022

Background

Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment.

Methods

Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels.

Results

Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment.

Conclusions

Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement.

Trial registration Eudract: 2013-001356-36
Effects of short-term ambient PM2.5 exposure on cardiovascular disease incidence and mortality among U.S. hemodialysis patients: a retrospective cohort study
Authors: Xi Yuzhi , Richardson David B. , Kshirsagar Abhijit V. , Wade Timothy J. , Flythe Jennifer E. , Whitsel Eric A. , Peterson Geoffrey C. , Wyatt Lauren H. , Rappold Ana G.
Published: March 2022

Background

Ambient PM2.5is a ubiquitous air pollutant with demonstrated adverse health impacts in population. Hemodialysis patients are a highly vulnerable population and may be particularly susceptible to the effects of PM2.5exposure. This study examines associations between short-term PM2.5exposure and cardiovascular disease (CVD) and mortality among patients receiving maintenance in-center hemodialysis.

Methods

Using the United State Renal Data System (USRDS) registry, we enumerated a cohort of all US adult kidney failure patients who initiated in-center hemodialysis between 1/1/2011 and 12/31/2016. Daily ambient PM2.5exposure estimates were assigned to cohort members based on the ZIP code of the dialysis clinic. CVD incidence and mortality were ascertained through 2016 based on USRDS records. Discrete time hazards regression was used to estimate the association between lagged PM2.5exposure and CVD incidence, CVD-specific mortality, and all-cause mortality 1 t adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and comorbidities.

Results

Among 314,079 hemodialysis patients, a 10 µg/m3increase in the average lag 0–1 daily PM2.5exposure was associated with CVD incidence (HR: 1.03 (95% CI: 1.02, 1.04)), CVD mortality (1.05 (95% CI: 1.03, 1.08)), and all-cause mortality (1.04 (95% CI: 1.03, 1.06)). The association was larger for people who initiated dialysis at an older age, while minimal evidence of effect modification was observed across levels of sex, race, or baseline comorbidities.

Conclusions

Short-term ambient PM2.5exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM2.5-associated CVD events than younger hemodialysis patients.
Genome editing via non-viral delivery platforms: current progress in personalized cancer therapy
Authors: Lan Tianxia , Que Haiying , Luo Min , Zhao Xia , Wei Xiawei
Published: March 2022

Cancer is a severe disease that substantially jeopardizes global health. Although considerable efforts have been made to discover effective anti-cancer therapeutics, the cancer incidence and mortality are still growing. The personalized anti-cancer therapies present themselves as a promising solution for the dilemma because they could precisely destroy or fix the cancer targets based on the comprehensive genomic analyses. In addition, genome editing is an ideal way to implement personalized anti-cancer therapy because it allows the direct modification of pro-tumor genes as well as the generation of personalized anti-tumor immune cells. Furthermore, non-viral delivery system could effectively transport genome editing tools (GETs) into the cell nucleus with an appreciable safety profile. In this manuscript, the important attributes and recent progress of GETs will be discussed. Besides, the laboratory and clinical investigations that seek for the possibility of combining non-viral delivery systems with GETs for the treatment of cancer will be assessed in the scope of personalized therapy.
Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report
Authors: Ponzini Francesca , Kowal Luke , Ghafoor Mariam , Goldberg Allison , Chan Joanna , Lamm Ryan , Cannaday Shawnna M. , Richard Scott D. , Nevler Avinoam , Lavu Harish , Bowne Wilbur B. , Rosenblum Norman G.
Published: March 2022

Background

Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered.

Case Presentation

Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

Conclusions

Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.
A novel inflammation-related prognostic biomarker for predicting the disease-free survival of patients with colorectal cancer
Authors: Cai Xiaoling , Chen Fa , Liang Lisheng , Jiang Weizhong , Liu Xing , Wang Dong , Wu Yunli , Chen Jinyan , Guan Guoxian , Peng Xian-e
Published: March 2022

Background

To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients.

Methods

A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs).

Results

During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32–0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735,P< 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making.

Conclusions

Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.
Transcriptomic characterization of tissues from patients and subsequent pathway analyses reveal biological pathways that are implicated in spastic ataxia
Authors: Kakouri Andrea C. , Votsi Christina , Oulas Anastasis , Nicolaou Paschalis , Aureli Massimo , Lunghi Giulia , Samarani Maura , Compagnoni Giacomo M. , Salani Sabrina , Di Fonzo Alessio , Christophides Thalis , Tanteles George A. , Zamba-Papanicolaou Eleni , Pantzaris Marios , Spyrou George M. , Christodoulou Kyproula
Published: March 2022

Background

Spastic ataxias (SAs) encompass a group of rare and severe neurodegenerative diseases, characterized by an overlap between ataxia and spastic paraplegia clinical features. They have been associated with pathogenic variants in a number of genes, including GBA2. This gene codes for the non-lysososomal β-glucosylceramidase, which is involved in sphingolipid metabolism through its catalytic role in the degradation of glucosylceramide. However, the mechanism by which GBA2 variants lead to the development of SA is still unclear.

Methods

In this work, we perform next-generation RNA-sequencing (RNA-seq), in an attempt to discover differentially expressed genes (DEGs) in lymphoblastoid, fibroblast cell lines and induced pluripotent stem cell-derived neurons derived from patients with SA, homozygous for the GBA2 c.1780G > C missense variant. We further exploit DEGs in pathway analyses in order to elucidate candidate molecular mechanisms that are implicated in the development of the GBA2 gene-associated SA.

Results

Our data reveal a total of 5217 genes with significantly altered expression between patient and control tested tissues. Furthermore, the most significant extracted pathways are presented and discussed for their possible role in the pathogenesis of the disease. Among them are the oxidative stress, neuroinflammation, sphingolipid signaling and metabolism, PI3K-Akt and MAPK signaling pathways.

Conclusions

Overall, our work examines for the first time the transcriptome profiles of GBA2-associated SA patients and suggests pathways and pathway synergies that could possibly have a role in SA pathogenesis. Lastly, it provides a list of DEGs and pathways that could be further validated towards the discovery of disease biomarkers.
Association between insomnia and subclinical atherosclerosis among Chinese steelworkers: a cross-sectional survey
Authors: Wang Lihua , Zhang Shengkui , Yu Miao , Yuan Juxiang
Published: March 2022

Background

Insomnia is a common prevalent sleep disorder. Difficulty maintaining sleep or poor in quality in insomnia caused by disrupted or misaligned circadian rhythms may play an important role in the development of atherosclerosis. This study aimed to examine the association between insomnia and subclinical atherosclerosis in Chinese steelworkers.

Methods

A total of 3240 subjects from a large enterprise located in northern China were included in this study. The Athens Insomnia Scale (AIS) was used to assess the status of insomnia. Subclinical atherosclerosis was evaluated using ultrasonographic measurements of carotid plaque. Multivariable logistic regression was used to identify association between insomnia and carotid atherosclerosis.

Results

The overall prevalence of insomnia and carotid plaque were 35.3 and 31.7% in the study population. Compared with non-insomnia workers, significantly increased odds of carotid plaque were observed among insomnia workers after adjusting for potential confounders, odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.17 to 1.63. Exposure to current shift work and insomnia simultaneously can significantly elevated the odds of carotid plaque.

Conclusion

Insomnia is associated with elevated odds of carotid atherosclerosis in male steelworkers. Insomnia problems of workers should receive further attention in occupational worker health interventions.
Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study
Authors: Pei Yuanyuan , Zhou Guangping , Wang Pengfei , Shi Fang’e , Ma Xiaolu , Zhu Jihong
Published: March 2022

Background

Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients.

Methods

This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed.

Results

AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently.

Conclusion

Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.
Autologous treatment for ALS with implication for broad neuroprotection
Authors: Kim Daehwan , Kim Subin , Sung Ashley , Patel Neetika , Wong Nathan , Conboy Michael J. , Conboy Irina M.
Published: March 2022

Background

Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of motor neurons (MNs), leading to paralysis, respiratory failure and death within 2–5 years of diagnosis. The exact mechanisms of sporadic ALS, which comprises 90% of all cases, remain unknown. In familial ALS, mutations in superoxide dismutase (SOD1) cause 10% of cases.

Methods

ALS patient-derived human-induced pluripotent stem cells (ALS hiPSCs, harboring the SOD1AV4 mutation), were differentiated to MNs (ALS-MNs). The neuroprotective effects of conditioned medium (CM) of hESCs (H9), wt hiPSCs (WTC-11) and the ALS iPSCs, on MN apoptosis and viability, formation and maintenance of neurites, mitochondrial activity and expression of inflammatory genes, were examined. For in vivo studies, 200 μl of CM from the ALS iPSCs (CS07 and CS053) was injected subcutaneously into the ALS model mice (transgenic for the human SOD1G93A mutation). Animal agility and strength, muscle innervation and mass, neurological score, onset of paralysis and lifespan of the ALS mice were assayed. After observing significant disease-modifying effects, the CM was characterized biochemically by fractionation, comparative proteomics, and epigenetic screens for the dependence on pluripotency. CM of fibroblasts that were differentiated from the wt hiPSCs lacked any neuroprotective activity and was used as a negative control throughout the studies.

Results

The secretome of PSCs including the ALS patient iPSCs was neuroprotective in the H2O2 model. In the model with pathogenic SOD1 mutation, ALS iPSC-CM attenuated all examined hallmarks of ALS pathology, rescued human ALS-MNs from denervation and death, restored mitochondrial health, and reduced the expression of inflammatory genes. The ALS iPSC-CM also improved neuro-muscular health and function, and delayed paralysis and morbidity in ALS mice. Compared side by side, cyclosporine (CsA), a mitochondrial membrane blocker that prevents the leakage of mitochondrial DNA, failed to avert the death of ALS-MNs, although CsA and ALS iPSC-CM equally stabilized MN mitochondria and attenuated inflammatory genes. Biochemical characterization, comparative proteomics, and epigenetic screen all suggested that it was the interactome of several key proteins from different fractions of PSC-CM that delivered the multifaceted neuroprotection.

Conclusions

This work introduces and mechanistically characterizes a new biologic for treating ALS and other complex neurodegenerative diseases.
Psychometric properties and validation of the English version Giessen Subjective Complaints List (GBB-8)
Authors: Petrowski Katja , Zenger Markus , Schmalbach Bjarne , Bastianon Christina Diane , Strauss Bernhard
Published: March 2022

Background

The present study investigated the psychometric properties of the newly developed English version of the Giessen Subjective Complaint List-8 (GBB-8), a questionnaire assessing psychosomatic symptoms with regard to exhaustion, gastrointestinal, musculoskeletal and cardiovascular.

Methods

A U.S. sample of 638 participants (47.6% female) was recruited by MTurk to participate in this cross-sectional online survey. Validation instruments included the Patient Health Questionnaire-4, Perceived Stress Scale, short version of the Trier Inventory for Chronic Stress.

Results

Reliability was high with ω’s between .80 and .86 for all subscales. Confirmatory factor analyses yielded comparable good model fit for a four-dimensional model as well as a higher order model. Multi-group confirmatory factor analyses confirmed measurement invariance of the GBB-8 across sex and age. Regarding convergent validity, correlations with other instruments were highly significant and of large magnitude as expected.

Conclusion

The English version of the GBB-8 has shown excellent psychometric properties. Therefore, it can be recommended for the assessment of psychosomatic complaints in contexts where short screening instruments are necessary.
3D dynamic fashion design development using digital technology and its potential in online platforms
Authors: Choi Kyung-Hee
Published: March 2022

The purpose of this study is to develop 3D dynamic fashion garments with changeable styles, colors and textile patterns, especially using a 3D virtual simulation system, and to examine their potential possibilities in online fashion platforms. For designing and developing 3D dynamic fashion garments, CLO3D and Aftereffects were used with a design collaboration between a fashion designer and a motion graphic artist group. Ten samples of a ready-to-wear collection were developed to visualize aesthetic and technological explorations of 3D dynamic fashion garments, composed of short videos. This study also evaluated the potential of 3D dynamic fashion garments along with 3D virtual simulation systems through focus group interview with professional fashion designers and digital experts, which indicated social and industrial possibilities toward them. This survey showed a list of findings in terms of current status of 3D virtual simulation systems and their impact on companies, discourses on the uncanny valley surrounding avatars, changes in fashion design process derived from 3D virtual simulation systems, co-design and customization in online platforms, and future prospects of 3D virtual garments in the fashion and gaming industries. Finally, this study led to discussions on future possible digital fashion design with several implications, based on design criteria, including digital technology, dynamic range, wearability, expressivity, interactivity, sustainability, and context.
Problem of borderline hemoglobin A2 levels in an Iranian population with a high prevalence of α- and β-thalassemia carriers
Authors: Moradi Keivan , Alibakhshi Reza , Shafieenia Samaneh , Azimi Azam
Published: March 2022

Background

It is difficult to classify a small fraction of α- and β-thalassemia (α- and β-thal) carriers based on their Hb A2 levels. Here, we report the results of a molecular investigation in a cohort of thalassemia carriers with borderline Hb A2 levels originated from western Iran.

Results

The documents of 5956 α- or β-thal carriers were reviewed. The frequency of individuals with borderline Hb A2 levels in this cohort was 436 (7.32%). A total of 12 different α-thal and 27 different β-thal variants were identified in this study.

Conclusions

Our data showed that individuals with borderline Hb A2 are not uncommon in our population. Moreover, preselection of α- and β-thal carriers with borderline Hb A2 levels based on Hb A2, mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) is not advisable in our population. Therefore, it is necessary to investigate both α- and β-globin genes in cases with borderline Hb A2 levels, especially if the partner is a carrier of β-thal or α0-thal.
Utility of prognostic scores in predicting short-term mortality in patients with acute-on-chronic liver failure
Authors: Zakareya Talaat , Akl Mohamed , Shibl Shereen , El-Mazaly Mohamed , Abdel-Razek Wael
Published: March 2022

Background

Acute-on-chronic liver failure (ACLF) is a distinct syndrome associated with high short-term mortality. Early identification of patients at high risk is essential to determine emergency for transplantation and decide and prioritize the need for intensive care unit (ICU). We aimed to evaluate the performance of the different prognostic scores in the prediction of in-hospital mortality in patients with ACLF. A total of 249 patients with ACLF were included and followed till discharge from the hospital. Univariate and Cox regression analyses were used to assess the performance of liver-specific (Child-Pugh and MELD) and ACLF prognostic scores (CLIF-C OF, CLIF-SOFA, CLIF-C AD, CLIF-C ACLF) in the prediction of in-hospital mortality.

Results

Patients were mostly males (71.1%) with a mean age of 53.9 ± 12.8 years. The etiology of pre-existing liver disease was HCV in 57.8%. Sepsis was the most common precipitating factor (49.8%) and the mortality rate was 74.3%. In univariate analysis, all scores were significantly higher in the deceased group (P<0.0001). AUROC were 0.897, 0.884, 0.870, 0.861, 0.861, and 0.850 for CLIF-C OF, CLIF-C AD, CLIF-C ACLF, Child-Pugh, CLIF-SOFA, and MELD scores, respectively. In multivariate analysis, 2 independent predictors of mortality were identified: CLIF-C ACLF score (OR 3.25, 95% CI 1.03–10.25, P<0.0001) and Child-Pugh class C (OR 1.04, 95% CI 1.02–1.06, P=0.044).

Conclusions

All the studied scores could predict in-hospital mortality of patients with ACLF. However, CLIF-C ACLF and Child-Pugh class performed better as they could significantly and independently predict mortality.
Thermal and mechanical studies of nanochitosan incorporated polymethyl methacrylate-based composite electrolytes
Authors: Shyly P. M. , Ammakutti Sridevi N. , Sumithraj Premkumar P.
Published: March 2022

The composite solid polymer electrolytes based on Polymethyl methacrylate–Lithium triflate with nanochitosan as inert nanofiller were prepared by membrane hot-press method. Nanochitosan was synthesized from shrimp shell. The obtained polymer membrane was subjected to X-ray diffraction and Fourier transform infrared spectroscopy to study the structural behavior. X-ray diffraction studies revealed that the incorporation of nanochitosan in the prepared polymer matrix enhanced the amorphous phase. The complexation behavior of the prepared electrolytes was analyzed by Fourier transform infrared spectroscopy. Thermogravimetric and differential scanning calorimetric studies were carried out to understand the thermal stability of the prepared polymer composite electrode. The incorporation of nanochitosan in the polymer matrix significantly reduces the crystalline temperature of polymethyl methacrylate which was confirmed by differential scanning calorimetric study. Universal testing studies were carried to know the mechanical stability of the prepared solid polymer electrolytes. The ionic conductivity of the prepared composite polymer electrolyte was carried out using electrochemical impedance spectroscopy from ambient to 120 °C.
Serenity Integrated Mentoring and the High Intensity Network: a scheme that raises serious questions for practice and governance in UK psychiatry
Authors: House Allan
Published: March 2022

Serenity Integrated Mentoring (SIM) involved the police and mental health crisis services working in a single team, developing case management plans that allowed a seamless move from offers of therapeutic engagement (by the mental health team) to use of coercive measures (by the police) with those who persisted with frequent crisis presentations. Withdrawn after widespread criticism, the scheme raises important questions – about the practice of mental health professionals who are involved in decisions about using criminal sanctions for people presenting in crisis, about the ethical and legal status of the sharing of confidential clinical information with the police, and about the processes that professional bodies use in promoting, monitoring and responding to controversial service developments.
Trace of depression: Network structure of depressive symptoms in different clinical conditions
Authors: Yokoyama Satoshi , Okada Go , Takagaki Koki , Itai Eri , Kambara Kohei , Mitsuyama Yuki , Shinzato Hotaka , Masuda Yoshikazu , Jinnin Ran , Okamoto Yasumasa
Published: March 2022

Background

Psychopathological network model has received attention recently in the traditional debate about the continuity of depression. However, there is little evidence for comparing the network structure of depressive symptoms in several depressive states at different clinical stages. Through this study of a broad sample of patients with nonclinical to clinical depression, we examined differences in the network structure of depressive symptoms.

Methods

Four groups of participants, including cohorts of clinical depression (current depression,n = 294; remitted depression,n = 118) and nonclinical depression (subthreshold depression,N = 184; healthy control,n = 257), responded to Beck Depression Inventory-II (BDI-II). After adjusting for age and sex, the residual scores of the 21 BDI-II items were input into a regularized partial correlation network for each group. Then, the estimated edge strengths/densities and node characteristics were compared.

Results

Current depression has a discontinuous structure with a stronger and denser network of symptoms compared with nonclinical groups. Interestingly, remitted depression had improved to the level in healthy controls; however, it retained the same network structure as current depression, which indicates a trace of depression.

Conclusions

We found the traces of depression that remained even after the symptoms disappeared. This study might provide a novel framework for elucidating the development and formation of depression.
Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama
Authors: Salama Mahmoud , Ataman Lauren , Taha Tamer , Azmy Osama , Braham Marouen , Douik Fatma , Khrouf Mohamed , Rodrigues Jhenifer Kliemchen , Reis Fernando M. , Sánchez Flor , Romero Sergio , Vega Mario , Woodruff Teresa K.
Published: March 2022

Purpose

Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care.

Materials and Methods

To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed.

Results

Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs.

Conclusion

Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.
Maternal Testosterone Concentrations in Third Trimester and Offspring Handgrip Strength at 5 Years: Odense Child Cohort
Authors: Dybdahl Malene , Dalgård Christine , Glintborg Dorte , Andersen Marianne Skovsager , Christesen Henrik Thybo
Published: March 2022

Background

Maternal testosterone in pregnancy may have conditioning effects on offspring muscle strength.

Purpose

To investigate possible associations between maternal testosterone concentrations in third trimester and offspring handgrip strength (HGS) at 5 years.

Methods

In the prospective, population-based Odense Child Cohort, total testosterone (TT) at gestational week 27-28 and 5-year HGS were measured in 1017 mother-child pairs. TT was measured by liquid chromatography-tandem mass spectrometry and free testosterone (FT) was calculated from TT and sex hormone-binding globulin (SHBG). Multivariable regression analyses were performed with HGS < 10th percentile as cutoff for low HGS.

Results

Third-trimester FT concentration was 0.004 (0.002-0.007) nmol/L, geometric mean (mean − SD; mean + SD). The mean (SD) 5-year HGS was 8.7 (1.8) kg in boys and 8.1 (1.7) kg in girls (P < 0.001). Higher FT concentrations were associated with lower HGS (β = −0.186, P = 0.048), after adjustment for maternal age, parity, offspring sex, and 5-year height and weight. FT > 0.004 nmol/L was associated with higher risk of 5-year HGS < 10th percentile with odds ratios (95% CI) of 1.58 (1.01, 2.47; P = 0.047; n = 1,017) and 1.69 (1.05, 2.74; P = 0.032) after further adjustment for children’s organized sports in subgroup analysis (n = 848). Lower HGS in relation to higher FT concentrations was found in all linear models but was not always statistically significant. HGS was not associated with maternal TT and SHBG levels.

Conclusion

Third trimester FT was inversely associated with offspring muscle strength assessed by HGS at 5 years of age, which may suggest a negative effect of maternal FT on offspring muscle strength.
Corifollitropin Alfa Combined With Human Chorionic Gonadotropin in Adolescent Boys With Hypogonadotropic Hypogonadism
Authors: Shankar R Ravi , Shah Suneri , Joeng Hee-Koung , Mendizabal Geraldine , DiBello Julia R , Guan Yanfen , Stegmann Barbara J , Nieschlag Eberhard , Behre Hermann M , Swerdloff Ronald S , Fox Michelle C , Kaufman Keith D
Published: March 2022

Context

Adolescent males with hypogonadotropic hypogonadism (HH) have traditionally been treated with exogenous testosterone (T) or human chorionic gonadotropin (hCG) to produce virilization; however, those modalities do not result in growth of the testes and may promote premature maturation and terminal differentiation of Sertoli cells prior to their proliferation, which may impact future fertility. Another option is to use gonadotropins in those individuals to induce testicular growth, proliferation and maturation of Sertoli cells, and production of endogenous T with consequent virilization.

Objective

We examined the efficacy and safety of corifollitropin alfa (CFA) combined with hCG for the induction of testicular growth and pubertal development in adolescent boys with HH.

Methods

This was a 64-week, multicenter, open-label, single-group study of CFA in adolescent boys, aged 14 to younger than 18 years, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 μg if weight ≤ 60 kg, or 150 μg if weight > 60 kg) given subcutaneously once every 2 weeks, after which they entered a 52-week combined treatment period with CFA, once every 2 weeks, and subcutaneous hCG, twice-weekly (hCG dose adjusted between 500 IU and 5000 IU to keep total T and estradiol levels within protocol-specified ranges). The primary efficacy end point was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound.

Results

After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 (95% CI, 7.44-11.97) (arithmetic mean of change from baseline at week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies.

Conclusion

Treatment of adolescent boys with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased T, and a pubertal growth spurt (EudraCT: 2015-001878-18).
The Rise of Sonless Families in Asia and North Africa
Authors: Pandian Roshan K. , Allendorf Keera
Published: March 2022

A neglected consequence of declining fertility is the likely rise of families with children of one sex—only sons or only daughters. Increases in such families present important demographic shifts that may weaken patrilineal family systems. We assess whether sons-only and daughters-only families rose in Asia and North Africa from the early 1990s to around 2015. Using 88 surveys and two censuses, we examine how the number and sex composition of children of mothers aged 40–49 changed across 20 countries, representing 87% of the region's population and 54% of the global population. We also compare observed trends to sex-indifferent counterfactuals, quantify contributions of fertility declines with decompositions, and investigate subnational trends in China and India. Increases in sons-only families were universal where numbers of children fell. Growth of daughters-only families was suppressed in patrilineal contexts, but these sonless families still rose significantly in 13 of 18 countries where numbers declined. By 2015, over a quarter of families in the region had only sons and nearly a fifth only daughters. There was considerable variation across countries: recent levels ranged from 28.3% to 3.4% daughters-only and from 40.1% to 6.0% sons-only. China and the rest of East Asia had the highest shares.
Gendered Struggles over the Medical Profession in the Modern Middle East and North Africa
Authors: Kozma Liat , Khayat Nicole
Published: March 2022

Historians of the professionalization of medicine in colonized regions, including the Middle East, have mostly focused on male practitioners, whereas histories of women in the medical professions are mostly centered in Western societies. The present issue examines histories of female medical practitioners by looking at case studies spanning the twentieth century from Algeria, Palestine, Israel, Iran, and Iraq. The introduction to this issue offers an overview of existing scholarship and charts sources and directions for future research and historical actors yet to be studied. The articles examine microlevel contact zones, in which women’s agency shaped and was shaped by colonial and postcolonial encounters, decolonization, and the formation of national professions. They reveal tensions within the medical sphere, between men and women, foreign and local, colonizer and colonized.