bluuebunny/crossref_metadata_2025 huggingface dataset:
Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology
Authors: D’Souza Alysha C. , Wageh Mai , Williams Jennifer S. , Colenso-Semple Lauren M. , McCarthy Devin G. , McKay Alannah K. A. , Elliott-Sale Kirsty J. , Burke Louise M. , Parise Gianni , MacDonald Maureen J. , Tarnopolsky Mark A. , Phillips Stuart M.
Published: October 2023

Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.
Chronic Oral Administration of Aluminum Hydroxide Stimulates Systemic Inflammation and Redox Imbalance in BALB/c Mice
Authors: de Souza Ana Beatriz Farias , Kozima Erika Tiemi , Castro Thalles de Freitas , de Matos Natália Alves , Oliveira Michel , de Souza Débora Maria Soares , Talvani André , de Menezes Rodrigo Cunha Alvim , Cangussú Sílvia Dantas , Bezerra Frank Silva
Published: October 2023

The present study is aimed at investigating the long‐term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long‐term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL‐2 were observed in the lungs, lower levels of IL‐10 in the liver and small intestine, and decreased levels of IL‐6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long‐term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long‐term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance.
Analyzing the Evolution and Host Adaptation of the Rabies Virus from the Perspective of Codon Usage Bias
Authors: Li Gen , Chen Xuhong , Li Xin , Liang Yinyi , Li Xiaolong , Liang Weiheng , Yan Zhibin , Wang Yueming , Wang Yang , Luo Jun , Guo Xiao-Feng , Zhu Xiu-Tong
Published: October 2023

Rabies virus (RABV) is a highly pathogenic virus that causes a fatal disease in humans and other mammals, but the mechanism of its evolution, spread, and spillover remains unknown. In this study, we analyzed the codon usage pattern of 2,018 RABV full-length genome sequences from 79 countries collected between 1931 and 2021 to provide an insight into its molecular evolution and unravel its unknown host-adapted pattern. We found that RABV exhibited a weak codon usage bias, with a preference for the codons ending in A (28.10 ± 0.01) or U (26.43 ± 0.02). Moreover, natural selection plays a major role in shaping the codon usage bias of the RABV. Notably, nearly half of the 18 codons in the virus were best matched to the hosts’ most abundant isoacceptor tRNAs, which might account for the wide range of RABV hosts. Furthermore, significant differences were observed in the codon usage patterns of RABV for different host species, suggesting that codon usage bias may be influenced by host-specific factors. In conclusion, our study reveals codon usage patterns of RABV that may help in the development of control strategies and effective vaccines and therapies against this deadly virus.
The Incidence of Infection Complicating Snakebites in Tropical Australia: Implications for Clinical Management and Antimicrobial Prophylaxis
Authors: Smith Laura K. , Vardanega John , Smith Simon , White Julian , Little Mark , Hanson Josh
Published: October 2023

Objective. To define the incidence of infection following snakebite in tropical Australia and the resulting implications for the routine prescription of prophylactic antibiotics. Methods. A retrospective study of all individuals presenting to Cairns Hospital, a tertiary referral hospital in tropical Australia, after a snakebite between December 2013 and October 2020. Results. There were 732 hospitalisations, 720 (98.4%) patients presented within 8 hours of the snakebite, and 29/732 (4.0%) were envenomated. Envenomated patients were more likely to receive empirical antibiotics than nonenvenomated patients (8/29 (27.6%) versus 14/703 (2.0%),

p
<
0.001

), although this was frequently as a bundle of care for critically ill individuals. Superficial skin infection was diagnosed by clinicians in 6/732 (0.8%) patients during their hospitalisation; infection was diagnosed more commonly in envenomated than in nonenvenomated patients (3/29 (10.3%) versus 3/703 (0.4%),

p
=
0.001

). All 3 envenomated individuals diagnosed with infection were believed to have taipan (genus Oxyuranus) bites. Five (83%) of the six patients diagnosed with infection had received empirical antibiotics at presentation; only 1/710 (0.1%) patients who received no antibiotics developed a (superficial) infection. Conclusion. Infection is a very uncommon complication of snakebite in tropical Australia. Individuals bitten by snakes in tropical Australia should not routinely receive antibiotic prophylaxis.
A Robust Symbol-Level Precoding Method for Multibeam Satellite Systems
Authors: Wang Qi , Zhou Wuyang
Published: October 2023

Compared to interference mitigating precoding, interference exploiting symbol-level precoding (SLP) requires less transmit power to guarantee the quality of service in a multibeam satellite system. However, due to the large roundtrip time (RTT), it is impractical to obtain real-time channel state information on the satellite side. The random channel state information (CSI) phase error of outdated CSI could cause serious performance deterioration of SLP. To compensate the CSI phase error, we propose an outdated CSI-based robust SLP (RSLP) method, which optimizes the transmit power under outage probability constraints. The central limit theorem (CLT) and second-order Taylor expansion are used to relax the outage probability constraints into convex ones. In addition, because only outdated CSI-based robust block-level precoding exists, we present two comparative RSLP methods accordingly. Without violating outrage probability constraints, the proposed RSLP method requires much lower transmit power than comparative RSLP and existing robust block-level precoding methods. The complexity of the proposed RSLP method is also lower than that of two comparative RSLP methods.
Targeting Cartilage miR-195/497 Cluster for Osteoarthritis Treatment Regulates the Circadian Clock
Authors: Shi Shi , Zhang Lele , Wang Qi , Wang Qian , Li Dejian , Sun Wei , Yi Chengqing
Published: October 2023

Introduction: Osteoarthritis (OA) is the most prevalent and debilitating joint disease without an effective therapeutic option. Multiple risk factors for OA have been identified, including abnormal chondrocyte miRNA secretion and circadian rhythms disruption, both of which have been found to cause progressive damage and loss of articular cartilage. Environmental disruption of circadian rhythms in mice predisposes animals to cartilage injury and OA. Methods: The role of miR-195/497 cluster during OA progression was verified by mouse OA model with intra-articular injection of Agomir and Antagomir. We performed micro-CT analysis, Osteoarthritis Research Society International scores, and histological analysis in mouse knee joints. RNA sequencing was performed on the mouse cartilage cell line to explore the molecular mechanism of the miR-195/497 cluster and proteins in signaling pathway were evaluated using Western blot. Senescence-associated phenotypes were detected by Western blot, senescence β-galactosidase staining, and immunofluorescence. Results: This study demonstrated that miR-195/497-5p expression is disrupted in OA with senescent chondrocytes. In addition, miR-195/497-5p influenced the circadian rhythm of mice chondrocytes by modulating the expression of the Per2 protein, resulting in the gradual degradation of articular cartilage. We found that the miR-195/497 cluster targets DUSP3 expression. The deletion of the miR-195/497 cluster increased the level of DUSP3 expression and decreased the levels of phosphorylated ERK 1/2 and CREB. Per2 transcription is upregulated by stimulating CREB and ERK 1/2 phosphorylation. Conclusion: Our findings identify a regulatory mechanism connecting chondrocyte miR-195/497-5p to cartilage maintenance and repair and imply that circadian rhythm disturbances affected by miR-195/497-5p are risk factors for age-related joint diseases such as OA.
Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation
Authors: Minculescu Lia , Reekie Joanne , Petersen Soeren Lykke , Kornblit Brian Thomas , Schjoedt Ida , Andersen Niels Smedegaard , Andersen Lisbeth Pernille , Fischer-Nielsen Anne , Haastrup Eva Kannik , Friis Lone Smidstrup , Sengelov Henrik
Published: October 2023

Introduction: Donor lymphocyte infusion (DLI) is used to induce remission in patients who relapse after allogeneic stem cell transplantation (allo-HSCT). During the last decade, the hypomethylating agent Azacitidine has been used together with DLI for a synergistic graft-versus-leukemia (GVL) effect. Here, we report results of DLI/Azacitidine treatment from a retrospective single-center study. Methods: Fifty AML/MDS patients treated for relapse after allo-HSCT between 2001 and 2020 with DLI at the Department of Hematology, at Rigshospitalet, Copenhagen University Hospital were included for analyses. A subgroup of patients who obtained complete remission (CR) after reinduction chemotherapy, received DLI in combination with low-dose (32 mg/m2) Azacitidine. Results: Overall survival in all patients after DLI treatment was 59% at 2 years and 20% at 5 years. Relapse-free survival in patients in CR prior to DLI was 32% after 2 years and 7% after 5 years. In the DLI + low-dose-Azacitidine group, 5-year relapse-free survival was 40%. Conclusion: DLI remains an effective treatment in post-transplant relapse leaving one-fifth of patients’ long-term survivors. Our results support the concomitant use of low-dose Azacitidine in the future use of DLI in order to enhance the GVL effect of donor lymphocytes.
ПІДГОТОВКА СПЕЦІАЛІСТІВ ІЗ БІОЛОГІЧНОЇ БЕЗПЕКИ ТА БІОЛОГІЧНОГО ЗАХИСТУ ЯК КЛЮЧОВА УМОВА ВІДПОВІДНИХ ДІЄВИХ ЗАХОДІВ
Authors: Величко М. В. , Андрейчин М. А.
Published: October 2023

Наведено основні докази украй важливого значення біологічної безпеки та захисту в збереженні благополуччя країни, особливо в умовах війни. Різним аспектам вирішення цієї проблеми присвячено численні праці українських і зарубіжних учених.

Метою роботи було проаналізувати важливі рішення органів центральної влади України щодо здійснення заходів із біологічної безпеки і біологічного захисту держави та обґрунтувати необхідність підготовки відповідних спеціалістів.

Результати вивчення відповідних законів України, рішень Кабінету Міністрів і Ради національної безпеки та оборони, у тому числі Стратегії забезпечення біологічної безпеки та біологічного захисту на період до 2025 року, свідчать, що вони загалом регулюють медико-біологічну діяльність у цьому напрямку. Водночас, на думку авторів статті, необхідно започаткувати нову спеціальність з метою підготовки фахівців для протидії загрозам біологічного характеру та відкрити її паспорт.
The Consequences of the Faulty Transmission of Sefer Tagin
Authors: Michaels Marc
Published: October 2023

Scribes are encouraged to maintain the tradition concerning the decorative tagin (tittles) and “strange” letter forms that adorn nearly two thousand letters in the Torah. Yet this tradition, detailed in Sefer Tagin, was relatively rarely followed and has all but died out in modern times. This article examines the faulty transmission of this Masoretic manual for sofrim (scribes) through core, compiled, and partial sources. It assesses the likely negative impact of its deployment through diversity caused by the transition to paraša format, error and innovation, and combination with other scribal rules.
The Holiness of Riẓba: A Study of a Rabbinic Historiography
Authors: Yahalom Shalem
Published: October 2023

This study deals with the public declaration by the Tosaphist R. Yitzhak ben Abraham (Riẓba) about his inability to consummate his marriage during its first few years. Ephraim Urbach, the great mid-twentieth century Jewish historian, considered this confession to be an expression of holiness and purity and to the ability to dissociate sexuality from feelings of guilt and shame. This assessment reflects the pretensions of Judaic studies of the era to understand the characters and predilections of rabbinic figures at a remove of hundreds of years. This paper rejects Urbach’s conclusions, maintaining that the compunctions associated with nudity and sexuality are modern phenomena. In medieval Europe, men and women bathed together, and this practice was considered perfectly acceptable in both Jewish and non-Jewish circles. Likewise, the intimate lives of married couples were not private. Consequently, Riẓba’s disclosure does not attest to his being holy or pure to an unusual degree.
“How Would He Not Protest God’s Putting to Death the Righteous Child?”
Authors: Lawee Eric
Published: October 2023

Medieval Jewish readings of the Akedah, the Binding of Isaac, remain almost entirely oblivious to the antinomy between ethics and the revealed divine command that many modern interpretations find at the heart of the story. This study explores an exception, the teaching of the fourteenth-century rationalist, Eleazar Ashkenazi ben Nathan Ha-Bavli. In his Revealer of Secrets, Eleazar seeks a remedy for what he takes to be the theological and moral scandals that arise when the Akedah is read according to its plain sense. While Eleazar’s treatment of the Akedah builds in many ways on that of Maimonides, it also adds novel layers regarding this most difficult of biblical accounts. For this reason, the study begins with a substantial review of Maimonides’ intentionally elusive treatment of the Akedah and its reception among some representative later medieval interlocutors. Turning to its main focus, the article supplies a case study in medieval Jewish rationalism at its limits, in both matter and manner.
A survey of the Sumatran Ctenidae (Araneae). 1. Two new Acantheis species
Authors: FOMICHEV ALEXANDER A. , OMELKO MIKHAIL M. , MARUSIK YURI M.
Published: October 2023

Two new species of Acantheis Thorell, 1891 are described from Sumatra Island: A. andreimishenini sp. n. (♂♀) and A. sergeimishenini sp. n. (♂). Detailed descriptions, digital photographs and a distributional map are provided. Male copulatory organs and habitus of A. dimidiatus (Thorell, 1890) from the same island are shown for the first time. The male and female copulatory organs of Acantheis are described in detail for the first time.
Description of a new species of Dixella from a cloud forest in Tlanchinol, Hidalgo and first record of Dixella aliciae (Johannsen) in Mexico (Diptera: Dixidae)
Authors: HUERTA HERÓN , IBÁÑEZ-BERNAL SERGIO
Published: October 2023

We present the first record of Dixella aliciae (Johannsen) in Mexico, collected in the locality of Lagunas de Zempoala National Park, Morelos state. Additionally, a new species of the genus Dixella Dyar & Shannon, Dixella machiotla sp. nov., is described and illustrated; specimens were collected in a cloud forest at an altitude of 1750 meters, in the Municipality of Tlanchinol, Hidalgo state. This new species is characterized by the shape of the gonostylus, with its distinctive digitiform mesially directed process, and dark brown katepisternum, with a small pale spot in the middle of the posterior margin.
A contribution to knowledge of Procloeon Bengtsson, 1915 from the Chinese mainland (Ephemeroptera: Baetidae) with description of a new species
Authors: CHEN XIAO-FANG , ZHOU CHANG-FA
Published: October 2023

The mayflies of the genus Procloeon Bengtsson, 1915 are common insects in China. However, partially because of its complicated taxonomic history and numerous species, this genus has never been revised locally in China. Here, we review all reported and related species from the Chinese mainland and confirmed three species of Procloeon occurred namely, Procloeon pennulatum (Eaton, 1870) (= Centroptilum henanensis Zhou et al., 1997, syn. n.) distributed in northern China, P. chinensis (She et al., 1995) (comb. nov.) from southern China and P. strumiferum sp. n. found in eastern China. The imagoes of the new species lack a costal projection of the hindwings but the gills I–V of the nymphs have double lamellae. In contrast, both the former species have costal process in the hindwings and double lamellae of gills I–VI. The three species can all be differentiated by imaginal genitalia and nymphal color. This revision clarifies all historical species in the genus Procloeon and Centroptilum from the Chinese mainland and provides a base for further research.
Description of Bolbolaimus major sp. nov. (Nematoda), from the Yellow Sea, China and phylogenetic analysis in Microlaimidae
Authors: WEN GUO , HUIXIN LIANG , YANWEI LV , CHUNMING WANG
Published: October 2023

Bolbolaimus major sp. nov. is described from Rizhao coast along the Yellow Sea. The new species is characterized by relatively large body size, cuticle strongly annulated, six outer labial sensilla setiform, four cephalic setae long, buccal cavity wide with one large dorsal tooth and two small subventral teeth, amphidial fovea unispiral shaped oval in males and circular in females, spicules curved with swollen proximal end, gubernaculum with anterior-hooked dorso-caudal apophysis, and tail conical with short spinneret. A phylogenetic analysis of maximum-likelihood and Bayesin inference based on rDNA sequences confirms the taxonomic position of Bolbolaimus major sp. nov. within the family Microlaimidae. Tree topology in Microlaimidae shows genus Microlaimus as polyphyletic group and genera in Microlaimidae are closely related.
Ant-mimicking thrips of the genus Compsothrips Reuter from China(Phlaeothripidae, Idolothripinae)
Authors: DANG LIHONG , GUO FUZHEN , AN YIYAN , MOUND LAURENCE A.
Published: October 2023

Species of Compsothrips are ant-mimics in body form and structure. In contrast to the predatory species of ant-mimicking Aeolothripidae, these species feed by ingesting fungal spores. Worldwide, there are 27 species listed in this genus, with three recorded here from China. Compsothrips tenebronus is here considered a new synonym of C. sinensis, and C. timur is newly recorded from China in Tibet. Furthermore, C. reticulates is redescribed, with details of the female given for the first time. An illustrated key is provided to the three species of Compsothrips from China.
Contribution to the subfamily Rhaphidophorinae Walker, 1869 in China (Orthoptera: Rhaphidophoridae) VI: One new species of Rhaphidophora from Guangxi Zhuang Autonomous Region
Authors: LI SHAN , BIAN XUN
Published: October 2023

In this paper, we describe one new species based on the specimens from Guangxi Zhuang Autonomous Region, China. Descriptions and illustrations of the new species are provided. All the specimens are deposited in Guangxi Normal University.
TRADITIONAL BELIEFS AND ELECTORAL BEHAVIOR
Authors: Pelizzo Riccardo , Koepko Moise , Kuzenbayev Nygmetzhan , Kinyondo Abel
Published: October 2023

The party system literature has generally paid little attention to whether traditional beliefs have any impact on voters’ electoral behavior and the stability of party systems. The purpose of the present study shows that the stability of party systems and the pervasiveness of traditional beliefs go hand‐in‐hand. This article is expected to advance the scholarly understanding of the political consequences of traditional beliefs by showing that voters who hold traditional beliefs or engage in traditional practices are not simply less likely to have pro‐democratic attitudes or have a greater appreciation of dictatorial rule, but also more likely to vote for ruling parties in elections. The evidence presented in the article sustains a basic claim; namely, that the pervasiveness of traditional beliefs in Togolese society should be regarded as one of the determinants of the party system's stability.
Unbiased image segmentation assessment toolkit for quantitative differentiation of state-of-the-art algorithms and pipelines
Authors: Goyal Vishakha , Schaub Nick J. , Voss Ty C. , Hotaling Nathan A.
Published: October 2023

Background

Image segmentation pipelines are commonly used in microscopy to identify cellular compartments like nucleus and cytoplasm, but there are few standards for comparing segmentation accuracy across pipelines. The process of selecting a segmentation assessment pipeline can seem daunting to researchers due to the number and variety of metrics available for evaluating segmentation quality.

Results

Here we present automated pipelines to obtain a comprehensive set of 69 metrics to evaluate segmented data and propose a selection methodology for models based on quantitative analysis, dimension reduction or unsupervised classification techniques and informed selection criteria.

Conclusion

We show that the metrics used here can often be reduced to a small number of metrics that give a more complete understanding of segmentation accuracy, with different groups of metrics providing sensitivity to different types of segmentation error. These tools are delivered as easy to use python libraries, command line tools, Common Workflow Language Tools, and as Web Image Processing Pipeline interactive plugins to ensure a wide range of users can access and use them. We also present how our evaluation methods can be used to observe the changes in segmentations across modern machine learning/deep learning workflows and use cases.
Genetic factors, adherence to healthy lifestyle behaviors, and risk of bladder cancer
Authors: He Qiangsheng , Wu Siqing , Zhou Ying , Liu Yuchen , Xia Bin , Li Wenjing , Zhao Jinyu , Mi Ningning , Xie Peng , Qin Xiwen , Yuan Jinqiu , Pan Yihang
Published: October 2023

Background

Genetic and lifestyle factors both contribute to the pathogenesis of bladder cancer, but the extent to which the increased genetic risk can be mitigated by adhering to a healthy lifestyle remains unclear. We aimed to investigate the association of combined lifestyle factors with bladder cancer risk within genetic risk groups.

Methods

We conducted a prospective study of 375 998 unrelated participants of European ancestry with genotype and lifestyle data and free of cancer from the UK biobank. We generated a polygenic risk score (PRS) using 16 single nucleotide polymorphisms and a healthy lifestyle score based on body weight, smoking status, physical activity, and diet. Cox models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of genetic and lifestyle factors on bladder cancer.

Results

During a median follow-up of 11.8 years, 880 participants developed bladder cancer. Compared with those with low PRS, participants with intermediate and high PRS had a higher risk of bladder cancer (HR 1.29, 95% CI 1.07–1.56; HR 1.63, 95% CI 1.32–2.02, respectively). An optimal lifestyle was associated with an approximately 50% lower risk of bladder cancer than a poor lifestyle across all genetic strata. Participants with a high genetic risk and a poor lifestyle had 3.6-fold elevated risk of bladder cancer compared with those with a low genetic risk and an optimal lifestyle (HR 3.63, 95% CI 2.23 –5.91).

Conclusions

Adhering to a healthy lifestyle could substantially reduce the bladder cancer risk across all genetic strata, even for high-genetic risk individuals. For all populations, adopting an intermediate lifestyle is more beneficial than a poor one, and adhering to an optimal lifestyle is the ideal effective strategy for bladder cancer prevention.
A real-world analysis of trametinib in combination with hydroxychloroquine or CDK4/6 inhibitor as third- or later-line therapy in metastatic pancreatic adenocarcinoma
Authors: Tang Hui , Ge Yuping , You Tingting , Li Xiaoyuan , Wang Yingyi , Cheng Yuejuan , Bai Chunmei
Published: October 2023

Background

There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC.

Methods

Patients with mPDAC who received the combination of trametinib and HCQ or CDK4/6 inhibitors as third- or later-line therapy were reviewed. The efficacy and prognosis were further analyzed.

Results

A total of 13 mPDAC patients were enrolled, of whom 8 and 5 patients were treated with trametinib plus HCQ or a CDK4/6 inhibitor (palbociclib or abemaciclib), respectively. All enrolled patients had either KRAS G12D or G12V mutations and had received a median of 3 prior lines of therapy (range, 2–6). The median trametinib treatment duration was 1.4 months. Of the 10 patients with measurable disease, only 1 patient achieved stable disease, and the remaining patients had progressive disease. Moreover, in patients treated with trametinib plus HCQ and a CDK4/6 inhibitor, the median progression-free survival was 2.0 and 2.8 months, respectively, and the median overall survival was 4.2 and 4.7 months, respectively. Moreover, 5 (50%) patients experienced grade 3–4 adverse events in 10 patients with available safety data.

Conclusions

The combination of trametinib and HCQ or CDK4/6 inhibitors may not be an effective later-line treatment for mPDAC, and the current preliminary findings need to be confirmed by other studies with larger sample sizes.
Non-meningeal, non-pulmonary cryptococcosis with limited posterior uveitis in a kidney organ transplant recipient with antibody-mediated rejection: a case report
Authors: Lu Yi-An , Lin Chun-Hsien , Chang Chia-Jen , Shu Kuo-Hsiung , Chung Mu-Chi , Chou Chien-Chih
Published: October 2023

Background

Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia.

Case presentation

We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis.

Conclusions

Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.
The role of loneliness and learning burnout in the regulation of physical exercise on internet addiction in Chinese college students
Authors: Wang Kun , Li Yan , Yang Yi , Zhang Tingran , Luo Jiong
Published: October 2023

Objective

To explore the mediating effects of physical exercise on internet addiction in Chinese college students and to reveal the mediating effects of loneliness and learning burnout on physical exercise and internet addiction.

Methods

1238 Chinese college students were investigated by physical exercise scale, loneliness scale, learning burnout scale, and internet addiction scale. The SPSS 27.0 was used to conduct a correlation analysis of the data and AMOS21.0 was used to establish a structural equation model to investigate the mediation effect.

Results

Physical exercise could directly negatively predict the internet addiction of college students. Loneliness and learning burnout partially mediate the relationship between physical exercise and internet addiction, and the mediating pathways included “physical exercise-loneliness-internet addiction”, “physical exercise-learning burnout-internet addiction”, and “physical exercise-loneliness-learning burnout-internet addiction”, accounting for 9.38%, 15.63% and 21.88% of the total effect, respectively. In the chain mediation effect, it was mainly the loneliness and sub-dimensions of learning burnout (low mood, misbehavior) that were at play.

Conclusion

Physical exercise not only directly affects internet addiction of college students but also indirectly affects internet addiction through the independent mediating effect of loneliness and learning burnout and the chain mediating effect of “loneliness-learning burnout”.
Mixed-methods cross-sectional study of the prevention of vertical HIV transmission program users unaware of male partner’s HIV status, in six South African districts with a high antenatal HIV burden
Authors: Mmotsa Tshiamo M. , Magasana Vuyolwethu , Nsibande Duduzile F. , Buthelezi Mbongeleni , Dassaye Reshmi , Rodriguez Violeta J. , Jones Deborah L. , Goga Ameena E. , Ngandu Nobubelo K.
Published: October 2023

Background

Elimination of vertical HIV Transmission (VHT) and maternal deaths are global health priorities. Male involvement is one of the most important factors that influences women’s decisions, including the uptake of Prevention of vertical HIV transmission (P-VHT). We sought to understand not knowing a male partner’s HIV status (MPHIVs) amongst women using services to prevent vertical HIV transmission in six South African districts with high antenatal HIV burden.

Methods

A mixed-methods cross-sectional study was conducted in six South African districts, and data collected through face-to-face interviews with women and focus group discussions (FGDs) with women or male partners. The quantitative data were analyzed using STATA SE-17.0 and an inductive approach was used for qualitative data analysis.

Results

Overall, 28.7% of women were unaware of their MPHIVs, while 25.3% and 46.0% knew the MPHIVs was positive or negative, respectively. In multivariable logistic regression, single marital status and unplanned pregnancy increased the odds of not knowing a MPHIVs while a woman’s disclosure of her HIV status to the male partner reduced the odds. FDGs highlighted complexities around MPHIVs disclosure, e.g., reluctance to test for HIV and potential interventions including healthcare worker (HCW) assisted HIV disclosure.

Conclusion

User-informed interventions to address MPHIVs non-disclosure amongst women of child-bearing age, particularly those at risk of unstable sexual partners and unplanned pregnancies, should be strengthened.
Plasma 8-OHdG act as a biomarker for steroid-induced osteonecrosis of the femoral head
Authors: Peng Peng , He Mincong , Fang Weihua , Lai Mengqi , Xiao Fangjun , He Wei , Xiao Huan , Wei Qiushi
Published: October 2023

Background

Oxidative stress was closely related to the occurrence and development of Steroid-induced osteonecrosis of the femoral head (SIONFH). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a important index of oxidative stress. The aim of this study is to investigate the role of 8-OHdG in the development of SIONFH.

Methods

From May 2021 and November 2021, 33 patients diagnosed with SIONFH and 26 healthy controls were recruited in this study. Assessment included the radiography and pathology evaluation of clinical bone tissue, expression position and level of 8-OHdG, level of plasma 8-OHdG, as well as the receiver operating characteristic (ROC) curve.

Results

We observed that expression levels of 8-OHdG in bone samples decreased with Association Research Circulation Osseous (ARCO) stages. Plasma 8-OHdG levels were significantly increased in the SIONFH group compared to the healthy control group. Plasma 8-OHdG level of pre-collapse patients was higher than that of post-collapse patients, the decreased plasma 8-OHdG level was related to higher ARCO stages.

Conclusion

Plasma 8-OHdG may represent potential biomarkers during SIONFH at different stages. Higher plasma 8-OHdG levels indicated early stage of SIONFH. The current study provided new clues for early diagnosis and treatment for SIONFH.
Comparison of short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis in laparoscopic total gastrectomy
Authors: Wu Chu-Ying , Lin Jian-An , Huang Qiao-Zhen , Xu Jian-Hua , Zhong Wen-Jin , Kang Wen-Gui , Wang Jin-Tian , Chen Jun-Xing , Zheng Hui-Da , Ye Kai
Published: October 2023

Background

To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy.

Methods

This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed.

Results

Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group.

Conclusions

Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.
Evaluating the effect of mechanical debridement with adjunctive antimicrobial photodynamic therapy in comparison with mechanical debridement alone on the peri-implant parameters in type 2 diabetic mellitus patients with peri-implantitis: a systematic review and meta-analysis
Authors: Afrasiabi Shima , Heidari Mohadeseh , Younespour Shima , Chiniforush Nasim
Published: October 2023

Background

Type 2 diabetes mellitus (T2DM) is a major risk factor for localized diseases such as peri-implantitis that may affect ideal implant treatment. This study was aimed to evaluate the effect of mechanical debridement (MD) + antimicrobial photodynamic therapy (a-PDT) in patients with peri-implantitis who have T2DM in terms of bleeding on probing (BOP) and probing depth (PD) as primary outcomes and plaque index (PI) and crestal bone loss (CBL) as secondary outcomes.

Methods

Publications compared outcomes between MD + aPDT and MD alone in T2DM patients with peri-implantitis, containing more than 3-month follow-up duration, were involved in the systematic review and meta-analysis. Literature until July 2023 using MEDLINE (through PubMed), Scopus, Cochrane Library, Embase, Web of Science, and Google Scholar were collected.

Results

Two randomized controlled trials (RCTs, 88 individuals) and one controlled clinical trial (CCT, 67 individuals) with follow-up periods ranged from 3 to 12 months were recruited. All studies used diode laser with wavelengths ranged from 660 to 810 nm. The results demonstrated that the MD + aPDT group showed significant benefits for BOP reduction after 6 months (SMD = -2.15, 95% CI: -3.78 to -0.51, p = 0.01). However, a great amount of heterogeneity was observed (I2 = 91.52%, p < 0.001). Moreover, there was a significant difference between MD + aPDT and MD alone groups in CBL (SMD = -0.69, 95% CI: -1.07 to -0.30, p < 0.001). In addition, homogeneity assumption was satisfied (I2 = 22.49%, p = 0.28). Significant differences in PD and PI reduction were not found except for PI reduction after 3 months (SMD = -0.79, 95% CI: -1.24 to -0.33, p < 0.001. Also, no heterogeneity was observed (I2 = 0.00%, p = 0.47).

Conclusion

Given that high heterogeneity in BOP and PD outcome was found in this systematic review, future long-term CTs with MD + aPDT should be examined to arrive at a firm conclusion.
Prevalence and factors associated with child marriage, a systematic review
Authors: Pourtaheri Asma , Sany Seyedeh Belin Tavakoly , Aghaee Monavvar Afzal , Ahangari Hamideh , Peyman Nooshin
Published: October 2023

Background

Girl child marriage is increasingly recognized as a critical barrier to global public health and gender discrimination. There are still more gaps in the global rate of child marriage and the underlying factors. Thus, the present systematic review aimed to explore the prevalence of child marriage and the underlying factors.

Methods

A comprehensive search was conducted for all English-language studies that measured the prevalence of child marriage and its correlates from 2000 to March 2022, indexed in PubMed, Scopus, Web of Science, Poplin, and Google Scholar databases. Child marriage is defined as marriage under the age of 18. In the present study, Joanna Briggs' quality assessment checklist was used for data collection. Two independent reviewers reviewed all the articles.

Results

In total, 34 eligible prevalence articles and 14 trend articles were included in the study with data from 127,945 participants. The prevalence of child marriage ranged between 1.8% to 90.85%. In most studies, the trend of child marriage was decreasing. The most important individual factors include the respondent's education and occupation, interpersonal factors such as the education and occupation of parents and husband, family size and type. Community factors include socioeconomic status, region, residence, ethnicity, and religion at the social level.

Conclusion

Despite a central focus of research and policies on interventions that decrease child marriage, this phenomenon is still prevalent in many places. Therefore, further specific interventions are required to improve education, reduce poverty and inequality. This may help achieve the 2030 Sustainable Development Goals.
An ex vivo model for education and training of unilateral cleft lip surgery
Authors: Lutz Rainer , Schulz Katja Leonie , Weber Manuel , Olmos Manuel , Möst Tobias , Bürstner Jan , Kesting Marco Rainer
Published: October 2023

Background

Unilateral cleft lip surgery is a complex procedure, and the outcome depends highly on the surgeon’s experience. Digital simulations and low-fidelity models seem inadequate for effective surgical education and training. There are only few realistic models for haptic simulation of cleft surgery, which are all based on synthetic materials that are costly and complex to produce. Hence, they are not fully available to train and educate surgical trainees. This study aims to develop an inexpensive, widely available, high-fidelity, ex vivo model of a unilateral cleft lip using a porcine snout disc.

Methods

A foil template was manufactured combining anatomical landmarks of the porcine snout disc and the anatomical situation of a child with a unilateral cleft. This template was used to create an ex vivo model of a unilateral cleft lip from the snout disc. Millard II technique was applied on the model to proof its suitability. The individual steps of the surgical cleft closure were photo-documented and three-dimensional scans of the model were analysed digitally. Sixteen surgical trainees were instructed to create a unilateral cleft model and perform a unilateral lip plasty. Their self-assessment was evaluated by means of a questionnaire.

Results

The porcine snout disc proved highly suitable to serve as a simulation model for unilateral cleft lip surgery. Millard II technique was successfully performed as we were able to perform all steps of unilateral cleft surgery, including muscle suturing. The developed foil-template is reusable on any porcine snout disc. The creation of the ex vivo model is simple and inexpensive. Self-assessment of the participants showed a strong increase in comprehension and an eagerness to use the model for surgical training.

Conclusions

A porcine snout disc ex vivo model of unilateral cleft lips was developed successfully. It shows many advantages, including a haptic close to human tissue, multiple layers, low cost, and wide and rapid availability. It is therefore very suitable for teaching and training beginners in cleft surgery and subsequently improving surgical skills and knowledge. Further research is needed to finally assess the ex vivo model’s value in different stages of the curriculum of surgical residency.
Making the match and breaking it: values, perceptions, and obstacles of trainees applying into physician-scientist training programs
Authors: Pepin M. E. , Kamal Y. , Reisman B. J. , Rockman M. E. , Waller J. P.
Published: October 2023

Background

Replenishing the physician-scientist workforce constitutes a central mission of medical education, but the loss of qualified trainees to non-academic positions remains an ongoing threat. Among the barriers facing physician-scientists today is the game-like model of U.S. medical residency matching through the National Research Matching Program (NRPM), which applies several assumptions regarding the comparability of applicant qualifications, cohort size, and the institutional breadth of applicants’ training needs.

Methods

The current report therefore summarizes the survey-based views and experiences of physician-scientist trainees obtained following the 2021–2022 application cycle for research-oriented residency programs, or physician-scientist training programs (PSTPs). From among this small cohort of applicants, we obtained survey-based feedback of 27 PSTP applicants across 17 U.S. medical universities, among whom 85% (23/27) matched into a PSTP.

Results

Among these PSTP applicants, 25/27 (93%) recognized “scientific community” as the most important feature of a postgraduate training program, with applicants identifying as female placing a higher value on the program’s infrastructure of personal and/or family support. Most (18/27) respondents found “waiting for interviews” as the most stressful phase of their application cycle, and roughly half of all respondents encountered at least one NRMP policy violation through post-interview communication. Specifically, 93% (25/27) respondents were contacted by at least one PSTP following interviews, and 1/3 of them admitted to feeling pressured into sharing their ranking preferences.

Conclusion

We highlight many previously unrecognized priorities among applicants to PSTPs, which include fostering community among its trainees and reinforcing structured mentoring. We uncover an inconsistency among PSTPs regarding the post-interview process, which represents an opportunity to better support applicants seeking to gauge programs according to their clinical, scientific, and academic interests as physician-scientists, while still adhering to NRMP policies.