bluuebunny/crossref_metadata_2025 huggingface dataset:
Courtship performance, not ornamentation, predicts mating success in two sister-species of wolf spider with divergent phenotypes
Authors: Hebets Eileen A. , Oviedo-Diego Mariela , Abdallah Abdallah , Griger Seth , McGinley Rowan , Starrett James , Bond Jason E. , Bern Mitch
Published: August 2024

Mate choice is posited to explain the evolution and maintenance of numerous secondary sexual traits, including ornamentation. This study explores the role of ornamentation in the mating success of two sister-species of wolf spider with divergent ornamentation. Mature male Schizocosa crassipalpata lack ornamentation while males of its closest living relative, S. bilineata, express both dark pigmentation and foreleg brushes. Following phenotypic manipulations of foreleg ornamentation – i.e. adding ornamentation in the form of dark pigment to non-ornamented males (S. crassipalpata, Aim 1) and removing ornamentation in varying degrees from highly ornamented males (S. bilineata, Aim 2 – shaving brushes; Aim 3 – shaving brushes and painting over dark pigment in vibration present/absent environments) – we found no evidence that ornamentation alone improves male mating success in either species, regardless of the vibratory signaling environment. In both S. bilineata experiments, however, higher courtship rates resulted in higher mating success, suggesting selection for courtship performance. Furthermore, females were more likely to turn, a presumed receptivity display, in response to males that courted at a higher rate. Also, similar to findings in another relative (S. stridulans), we found indications that ornamentation may function to ease a male’s reliance on courtship performance – i.e., at low courtship rates, only ornamented males can secure a mating. Our phenotypic manipulations also influenced courtship behavior in S. bilineata. Shaved males began courting earlier and courted more often over a longer time than intact males, yet ultimately acquired similar matings. This increased courtship effort likely compensated for reduced ornamentation. Finally, the vibratory environment appears crucial for female–male dialogue in S. bilineata, as vibratory absent environments resulted in increased female attacks and decreased male courtship rates. Together, our data suggest that S. crassipalpata females do not possess a preference for ornamentation and that S. bilineata females do not use ornamentation alone in mating decisions. Instead, our results are consistent with a hypothesis that ornamentation in Schizocosa evolved, and is likely maintained, due to its interactions with dynamic movement displays (i.e. leg movements), which can themselves be plastically altered based on the signaler’s phenotype as well as the signaling environment.
Novel PTPRQ variants associated with hearing loss in a Chinese family PTPRQ variants in Chinese hearing loss
Authors: Hou Yuan , Shi Yuanzhen , Liu Longyan , Duan Shihong
Published: August 2024

Introduction

Hearing loss is one of the most prevalent congenital sensory disorders. Over 50% of congenital hearing loss cases are attributed to genetic factors. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q, which plays an important role in maintaining the structure and function of the stereocilia of hair cells. Variants in the PTPRQ gene have been implicated in hereditary sensorineural hearing loss.

Methods and Results

Utilizing next-generation sequencing technology, we identified novel compound heterozygous variants (c.977G>A:p.W326X and c.6742C>T:p.Q2248X) in the PTPRQ gene within a Chinese national lineage, marking the first association of these variants with hereditary sensorineural hearing loss.

Discussion

Our findings further emphasize the critical role of PTPRQ in auditory function and contribute to a more comprehensive understanding of PTPRQ-associated hearing loss mechanisms, aiding in clinical management and genetic counseling.
The role of IL-37 in gastrointestinal diseases
Authors: Wang Qiang , Zhang Guangrun , An Caiping , Hambly Brett D. , Bao Shisan
Published: August 2024

Gastrointestinal mucosal surface is frequently under challenge due to it’s the large surface area and most common entry of microbes. IL-37, an anti-inflammatory cytokine, regulates local and systemic host immunity. H. pylori infection leads to the inhibition of IL-37 in the gastric mucosa, contributing to heightened mucosal inflammation and destruction, thereby facilitating increased proliferation of H. pylori. Food allergy, due to immune dysregulation, also contribute to GI injury. On the other hand, elevated levels of IL-37 observed in gastric cancer patients align with reduced host immunity at the cellular and humoral levels, indicating that IL-37 may contribute to the development of gastric cancer via suppressing pro-inflammatory responses. While IL-37 provides protection in an IBD animal model, the detection of highly produced IL-37 in IBD patients suggests a stage-dependent role, being protective in acute inflammation but potentially exacerbates the development of IBD in chronic conditions. Moreover, elevated colonic IL-37 in CRC correlates with overall survival time and disease time, indicating a protective role for IL-37 in CRC. The differential regulation and expression of IL-37 between upper- and lower-GI organs may be attributed to variations in the microbial flora. This information suggests that IL-37 could be a potential therapeutic agent, depending on the stage and location.
Targeting amino acid-metabolizing enzymes for cancer immunotherapy
Authors: Grobben Yvonne
Published: August 2024

Despite the immune system’s role in the detection and eradication of abnormal cells, cancer cells often evade elimination by exploitation of various immune escape mechanisms. Among these mechanisms is the ability of cancer cells to upregulate amino acid-metabolizing enzymes, or to induce these enzymes in tumor-infiltrating immunosuppressive cells. Amino acids are fundamental cellular nutrients required for a variety of physiological processes, and their inadequacy can severely impact immune cell function. Amino acid-derived metabolites can additionally dampen the anti-tumor immune response by means of their immunosuppressive activities, whilst some can also promote tumor growth directly. Based on their evident role in tumor immune escape, the amino acid-metabolizing enzymes glutaminase 1 (GLS1), arginase 1 (ARG1), inducible nitric oxide synthase (iNOS), indoleamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase (TDO) and interleukin 4 induced 1 (IL4I1) each serve as a promising target for immunotherapeutic intervention. This review summarizes and discusses the involvement of these enzymes in cancer, their effect on the anti-tumor immune response and the recent progress made in the preclinical and clinical evaluation of inhibitors targeting these enzymes.
Patient preferences for inflammatory bowel disease treatments: protocol development of a global preference survey using a discrete choice experiment
Authors: Schoefs Elise , Vermeire Séverine , Ferrante Marc , Sabino João , Verstockt Bram , Avedano Luisa , De Rocchis Maria Stella , Sajak-Szczerba Magdalena , Saldaña Roberto , Straetemans Noortje , Vandebroek Martina , Janssens Rosanne , Huys Isabelle
Published: August 2024

Background

As the therapeutic landscape for inflammatory bowel disease (IBD) continues to expand, a need exists to understand how patients perceive and value different attributes associated with their disease as well as with current and emerging treatments. These insights can inform the development and regulation of effective interventions for IBD, benefiting various stakeholders including healthcare professionals, drug developers, regulators, Health Technology Assessment bodies, payers, and ultimately patients suffering from IBD. In response to this, the present patient preference study was developed with the aim to (1) determine the relative preference weights for IBD treatment and disease related attributes, and (2) explain how preferences may differ across patients with different characteristics (preference heterogeneity).

Methods

The patient preference study (PPS) was developed through an 8-step process, with each step being informed by an advisory board. This process included: (1) stated preference method selection, (2) attribute and level development (including a scoping literature review, focus group discussions, and advisory board meetings), (3) choice task construction, (4) sample size estimation, (5) survey implementation, (6) piloting, (7) translation, and (8) pre-testing. The resulting discrete choice experiment (DCE) survey comprises 14 attributes with between two and five varying levels. Participants will answer 15 DCE questions with a partial profile design, where each of the choice questions encompasses two hypothetical treatment profiles showing four attributes. Additionally, questions about patients' socio-demographic and clinical characteristics, as well as contextual factors are implemented. The survey is available in 15 different languages and aims to minimally recruit 700 patients globally.

Discussion

This protocol gives valuable insights toward preference researchers and decision-makers on how PPS design can be transparently reported, demonstrating solutions to remaining gaps in preference research. Results of the PPS will provide evidence regarding the disease and treatment related characteristics that are most important for IBD patients, and how these may differ across patients with different characteristics. These findings will yield valuable insights applicable to preference research, drug development, regulatory approval, and reimbursement processes, enabling decision making across the medicinal product life cycle that is aligned with the true needs of IBD patients.
Game-theoretic analysis of governance and corruption in China's pharmaceutical industry
Authors: Wang Xi , Zhang Tao , Gong Hanxiang , Li Jinghua , Wu Baoling , Chen Baoxin , Zhao Shufang
Published: August 2024

Introduction

With the rapid development of China's pharmaceutical industry, issues of corruption and regulatory effectiveness have become increasingly prominent, posing critical challenges to public health safety and the industry's sustainable development.

Methods

This paper adopts a bounded rationality perspective and employs a game-theoretic evolutionary approach to establish a tripartite evolutionary game model involving pharmaceutical companies, third-party auditing organizations, and health insurance regulatory agencies. It analyzes the stable strategies of the parties involved and the sensitivity of key parameters within this tripartite game system.

Results

The study reveals that adherence to health insurance regulations by pharmaceutical companies, refusal of bribes by third-party auditing organizations, and the implementation of lenient regulations by health insurance agencies can form an effective governance equilibrium. This equilibrium state contributes to reducing corruption in the pharmaceutical industry, balancing the interests of all parties, and promoting healthy industry development.

Discussion

Pharmaceutical companies must balance compliance costs against the risks of non-compliance benefits while maximizing profits; third-party auditing organizations need to choose between fulfilling their duties and accepting bribes, considering their economic benefits and professional reputation; health insurance regulatory agencies adjust their strategies between strict and lenient regulation to maximize social welfare. The paper suggests enhancing policy support, strengthening compliance supervision, improving audit independence, and adjusting regulatory strategies to optimize governance in the pharmaceutical industry. Additionally, the research highlights the role of collaborative efforts among the three parties in achieving sustainable governance. Furthermore, the study conducts a numerical simulation analysis to demonstrate the impact of various parameters on the evolutionary stability of the system, providing practical insights into the implementation of regulatory policies. This research offers new insights for policy formulation and governance in China's pharmaceutical sector, providing significant reference value for guiding the industry's sustainable development.
Effects of romosozumab combined with routine therapy on pain relief, disease progression and adverse reactions in patients with postmenopausal osteoporosis: a systematic review and meta-analysis
Authors: Gao Ge , Cui Jian , Xie Yuanyuan , Dong Jing
Published: August 2024

Background

Postmenopausal osteoporosis (PMOP) increases fracture risk in women. Though traditional treatments are slow to act, combining romosozumab with conventional therapy shows promise. Despite its growing use, studies on effectiveness are limited. This study aims to systematically evaluate the combined therapy’s impact on pain relief, disease progression, and adverse reactions in PMOP patients.

Methods

Databases including PubMed, EMBASE, ScienceDirect, and the Cochrane Library were searched from their inception to September 2023 to identify randomized controlled trials (RCTs) evaluating the role of romosozumab in PMOP. Random or fixed effect models were employed for statistical analysis. Two reviewers independently assessed the quality of the included studies and extracted the data. The meta-analysis was conducted using RevMan 5.4 software.

Results

Six RCTs with a total sample size of 17,985 cases were included. The incidence of vertebral fractures was compared and analyzed after 12 and 24 months of treatment. Romosozumab significantly reduced the incidence of vertebral fractures at 24 months (OR = 0.36; 95% CI: 0.35–0.52) but not at 12 months (OR = 0.39; 95% CI: 0.14–1.05). It was also associated with a decreased incidence of nonvertebral fractures (OR = 0.79; 95% CI: 0.66–0.94) and clinical fractures at 24 months (OR = 0.70; 95% CI: 0.59–0.82) compared to standard therapy. Romosozumab demonstrated a significant improvement in percentage change in bone mineral density (BMD) [mean difference (MD) = 10.38; 95% CI: 4.62–16.14] and in hip joint BMD (MD = 4.24; 95% CI: 2.92–5.56). There was no notable difference in adverse reactions compared to standard care (p > 0.05). Funnel plots displayed a predominantly symmetrical pattern, suggesting no evidence of publication bias in the selected literature.

Conclusion

Combining romosozumab with conventional therapy effectively treats PMOP, significantly reducing vertebral, non-vertebral, and clinical fractures while increasing BMD in the hip, femoral neck, and lumbar spine. However, further high-quality studies are needed for validation.
Case report: Solitary fibrous tumor of the paracervical uterus combined with vaginal wall adenocarcinoma
Authors: Zhang Xiaowei , Chen Jun , Du Junqiang , Ying Jiajia
Published: August 2024

Background

Solitary fibrous tumors are rare mesenchymal tumors that typically occur in the pleura. Solitary fibrous tumors of the uterine cervix are uncommon. We report the first case of a patient who underwent total hysterectomy for vaginal wall adenocarcinoma and was found to have a concurrent solitary fibrous tumor in the paracervical-uterus.

Case presentation

A 51-year-old woman was admitted to our hospital due to contact bleeding. A gynecological examination revealed nodules of 3.0 × 1.0 cm on the vaginal wall, and a colposcopy with biopsy revealed adenocarcinoma of the vaginal wall. After the recommended staging examinations, the patient underwent total hysterectomy, double adnexectomy, pelvic lymph node dissection, and vaginal wall resection. During surgery, a nodule measuring approximately 2 × 2 cm was found in the middle of the mass in the left paracervical region. Subsequent postoperative histopathological examination confirmed an solitary fibrous tumor of the uterine cervix with adenocarcinoma of the vaginal wall. The patient was followed up for 46 months after hospitalization, and no recurrence or distant metastases were observed.

Conclusion

In rare cases, solitary fibrous tumors may form large masses in the cervical or vaginal wall. They can easily be misdiagnosed as benign or malignant cervical tumors before and during surgery. Postoperative pathology and immunohistochemistry are helpful for diagnosis. Most solitary fibrous cervical tumors are benign, occasionally with low malignant potential, and surgical treatment is feasible and effective.
Distribution and comparative genomic analysis of antimicrobial gene clusters found in Pantoea
Authors: Kirk Ashlyn , Stavrinides John
Published: August 2024

Members of the bacterial genus Pantoea produce a variety of antimicrobial products that are effective against plant, animal, and human pathogens. To date, little is known about the distribution and evolutionary history of these clusters. We surveyed the public databases for the 12 currently known antibiotic biosynthetic gene clusters found across Pantoea strains to determine their distribution. We show that some clusters, namely pantocin B, PNP-3, and PNP-4 are found strictly in Pantoea, while agglomerin, andrimid, AGA, dapdiamide, herbicolin, PNP-1, PNP-2, PNP-5, and pantocin A, are more broadly distributed in distantly related genera within Vibrionaceae, Pectobacteriaceae, Yersiniaceae, Morganellaceae, and Hafniaceae. We evaluated the evolutionary history of these gene clusters relative to a cpn60-based species tree, considering the flanking regions of each cluster, %GC, and presence of mobile genetic elements, and identified potential occurrences of horizontal gene transfer. Lastly, we also describe the biosynthetic gene cluster of pantocin B in the strain Pantoea agglomerans Eh318 more than 20 years after this antibiotic was first described.
Regulatory T cells administration reduces anxiety-like behavior in mice submitted to chronic restraint stress
Authors: Cepeda Yamila , Elizondo-Vega Roberto , Garrido Camila , Tobar Catalina , Araneda Matías , Oliveros Patricia , Ordenes Patricio , Carril Claudio , Vidal Pía M. , Luz-Crawford Patricia , García-Robles María. A. , Oyarce Karina
Published: August 2024

Background

Major depression disorder (MDD) and anxiety are common mental disorders that significantly affect the quality of life of those who suffer from them, altering the person’s normal functioning. From the biological perspective, the most classical hypothesis explaining their occurrence relies on neurotransmission and hippocampal excitability alterations. However, around 30% of MDD patients do not respond to medication targeting these processes. Over the last decade, the involvement of inflammatory responses in depression and anxiety pathogenesis has been strongly acknowledged, opening the possibility of tackling these disorders from an immunological point of view. In this context, regulatory T cells (Treg cells), which naturally maintain immune homeostasis by suppressing inflammation could be promising candidates for their therapeutic use in mental disorders.

Methods

To test this hypothesis, C57BL/6 adult male mice were submitted to classical stress protocols to induce depressive and anxiety-like behavior; chronic restriction stress (CRS), and chronic unpredictable stress (CUS). Some of the stressed mice received a single adoptive transfer of Treg cells during stress protocols. Mouse behavior was analyzed through the open field (OFT) and forced swim test (FST). Blood and spleen samples were collected for T cell analysis using cell cytometry, while brains were collected to study changes in microglia by immunohistochemistry.

Results

Mice submitted to CRS and CUS develop anxiety and depressive-like behavior, and only CRS mice exhibit lower frequencies of circulating Treg cells. Adoptive transfer of Treg cells decreased anxiety-like behavior in the OFT only in CRS model, but not depressive behavior in FST in neither of the two models. In CRS mice, Treg cells administration lowered the number of microglia in the hippocampus, which increased due this stress paradigm, and restored its arborization. However, in CUS mice, Treg cells administration increased microglia number with no significant effect on their arborization.

Conclusion

Our results for effector CD4+ T cells in the spleen and microglia number and morphology in the hippocampus add new evidence in favor of the participation of inflammatory responses in the development of depressive and anxiety-like behavior and suggest that the modulation of key immune cells such as Treg cells, could have beneficial effects on these disorders.
The dissociation between pathological caloric testing and a normal video head impulse test helps differentiate between Menière’s disease, vestibular migraine, and other vestibular disorders: a confirmatory study in a large cohort of 2,101 patients
Authors: Mavrodiev Vergil , Strupp Michael , Vinck Anne-Sophie , van de Berg Raymond , Lehner Louisa
Published: August 2024

Vestibular migraine (VM) and Menière’s disease (MD) are characterized by episodes of vertigo of similar duration. It is well known that differentiation between both diseases is not always possible based only on the patient history, physical examination, and audiological testing. In addition, the quantification of the vestibular function can also be helpful since, among patients with MD, there is often a dissociation between a normal/pseudo-normal video head impulse test (vHIT) and reduced caloric testing. The goal of this confirmatory study was to determine the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of this dissociation to differentiate between MD and VM as well as between MD and other vestibular diseases. We performed a retrospective analysis of 2,101 patients. The examination group consisted of 1,100 patients; of these, 627 (57%) had MD according to the diagnostic criteria of the Bárány Society and 473 (43%) had VM. The comparison group consisted of 1,001 patients with other peripheral, central, or functional vestibular disorders. Statistical analysis revealed the following findings for the dissociation: MD vs. VM: specificity: 83.5%, sensitivity: 58.9%, PPV: 82.6%, and NPV: 60.5%, and MD vs. all other vestibular disorders (VM plus others): specificity: 83.5%, sensitivity: 58.9%, PPV: 60.3%, and NPV: 82.7%. The dissociation between a normal vHIT and a reduced caloric response is due to the high specificity and PPV suited for the differentiation between MD and VM. This part of the study confirms previous findings in a large cohort of patients. When it comes to differentiating between MD and all observed vestibular disorders, if there is no dissociation, the diagnosis of MD is unlikely.
Attraction is altered via modulation of the medial prefrontal cortex without explicit knowledge
Authors: Zorns Samantha , Sierzputowski Claudia , Ash Sydney , Skowron Molly , Minervini Anthony , LaVarco Adriana , Pardillo Matthew , Keenan Julian Paul
Published: August 2024

Previous studies have demonstrated that brain stimulation can alter an individual's physical appearance via dysregulation of the medial prefrontal cortex (MPFC). In this study, we attempted to determine if individuals who receive repetitive transcranial magnetic stimulation (rTMS) delivered to the MPFC were rated as more attractive by others. It has been previously reported that 1 hertz (Hz) (inhibitory) TMS can alter one's facial expressions such that frontal cortex inhibition can increase expressiveness. These alterations, detected by external observation, remain below the level of awareness of the subject itself. In Phase I, subjects (N = 10) received MPFC rTMS and had their photographs taken after each of the five stimulation conditions, in addition to making self-ratings across a number of variables, including attractiveness. In Phase II, participants (N = 430) rated five pictures of each of the Phase 1 individuals on attractiveness. It was found that there were no significant differences in self-assessment following rTMS (Phase I). However, attractiveness ratings differed significantly in Phase II. There was a significant difference found between 10 Hz TMS delivered to the MPFC (p < 0.001), such that individuals were rated as less attractive. Furthermore, 1 Hz TMS to the MPFC increased the number of ‘Most Attractive' ratings, while 10Hz TMS decreased the number of ‘Most Attractive' ratings (p < 0.001). These results suggest that the MPFC plays a role in attractiveness ratings to others. These data also support research showing that one's appearance can be altered below the level of awareness via rTMS. To our knowledge, this is the first investigation to examine how brain stimulation influences one's attractiveness.
Case Report: Application of 18F-FDG PET/CT in identifying plasmacytoma in monoclonal gammopathy associated peripheral neuropathy
Authors: Weng Jiequn , Lin Jie , Sun Chong
Published: August 2024

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes.
Genetic information supports a causal relationship between trace elements, inflammatory proteins, and COPD: evidence from a Mendelian randomization analysis
Authors: Cao Zhenghua , Zhao Shengkun , Wu Tong , Sun Feng , Ding Huan , Hu Shaodan , Shi Li
Published: August 2024

Objective

Dietary factors and nutritional status may be among the risk factors for Chronic Obstructive Pulmonary Disease (COPD). There exists a certain correlation between trace elements and COPD. Through Mendelian Randomization (MR) analysis, we investigated the causal relationships between trace elements, inflammatory proteins, and COPD.

Methods

We employed MR, multivariable MR (MVMR), and two-step MR (TSMR) approaches to assess the causal links between 15 trace elements and COPD, with 91 inflammatory proteins serving as mediators to further elucidate the tripartite causal relationships.

Results

Trace elements such as Folate (OR = 1.293, 95%CI 1.027–1.628; p = 0.029), Vitamin D (OR = 1.331, 95%CI 1.071–1.654; p = 0.010), Vitamin B12 (OR = 1.424, 95%CI 1.108–1.828; p = 0.006), and Iron (OR = 0.741, 95%CI 0.580–0.946; p = 0.016) demonstrated causal relationships with COPD. No causal relationship was observed in reverse MR. After adjusting for BMI, Folate (OR = 1.633, 95%CI 1.098–2.429; p = 0.015), Iron (OR = 0.507, 95%CI 0.31–0.778; p = 0.001), and Vitamin D (OR = 1.511, 95%CI 1.029–2.217; p = 0.034) were identified as independent risk factors for COPD, whereas Vitamin B12 (OR = 1.118, 95%CI 0.751–1.666; p = 0.581) was not. Mediation analysis indicated that CDCP1 (5.76%) may play a mediating role between Iron and COPD.

Conclusion

Trace elements such as Folate, Vitamin D, Vitamin B12, and Iron have causal relationships with COPD. After BMI adjustment, Folate, Vitamin D, and Iron emerge as independent risk factors. Furthermore, the inflammatory protein CDCP1 may partially mediate the causal relationship between Iron and COPD, offering a scientific basis for dietary recommendations that could benefit COPD patients. The supplementation of trace elements may be advantageous for individuals suffering from COPD.
Causal effect of lifestyle and metabolic indicator with herpes zoster: a two-sample Mendelian randomization study
Authors: Huang Mingsheng , Liu Yiheng , Chen Cheng , Dai Weiran
Published: August 2024

Background

Previous observational studies have reported certain causal relationships between factors such as smoking, alcohol consumption, obesity, physical activity, metabolic disorders, and the incidence of herpes zoster (HZ). However, there is controversy regarding the observed results across different studies. Our objective was to investigate the causal effects of these risk factors on the risk of herpes zoster through a Mendelian randomization analysis using two-sample bidirectional approaches.

Methods

We conducted two-sample bidirectional Mendelian randomization analyses to explore the causal relationships between different lifestyles, obesity assessment indices, metabolic indicators, and the risk of herpes zoster. All exposure and outcome data were sourced from publicly available data from genome-wide association studies.

Results

In the inverse-variance weighted (IVW) analysis, body mass index (BMI) (OR: 1.160, 95% CI: 1.030–1.307, p = 0.014), Body fat percentage (BFP) (OR: 1.241, 95% CI: 1.050–1.467, p = 0.011), and whole body fat mass (WBFM) (OR: 1.199, 95% CI: 1.057–1.362, p = 0.005) exhibited positive associations with the risk of HZ. However, usual walking pace (UWP) (OR: 0.498, 95% CI: 0.254–0.976, p = 0.042) demonstrated a significant negative correlation with HZ risk. Other factors including alcohol intake frequency, smoking initiation, smoking status, insomnia, and sleep duration did not show significant causal relationships with HZ.

Conclusion

Mendelian randomization studies revealed that BMI, BFP, and WBFM are risk factors for HZ. UWP showed a protective effect against HZ. These findings provide a straightforward method for evaluating future clinical practices aiming to develop personalized management strategies and assess high-risk populations for HZ.
An A2 β-casein infant formula with high sn-2 palmitate and casein phosphopeptides supports adequate growth, improved stool consistency, and bone strength in healthy, term Chinese infants: a randomized, double-blind, controlled clinical trial
Authors: Sheng Xiao-Yang , Mi Wiola , Yuan Qing Bin , Liu Bryan Yanwen , Carnielli Virgilio , Ning Yi Bing , Einerhand Alexandra W. C.
Published: August 2024

The aim of this randomized, double-blind, controlled trial was to examine the effects of infant formula on the growth, stool consistency, and bone strength of infants (n = 120) over a period of 4 months. The investigational group was fed an A2 β-casein cow’s milk infant formula containing casein phosphopeptides (CPP) and high sn-2 palmitate (54% of total palmitate at sn-2). The control group was fed a standard cow’s milk formula without CPP and with low sn-2 palmitate (29% of total palmitate at sn-2). The third group was fed human milk (HM) (n = 60). All three groups had similar baseline characteristics, and maintained similar BMI, sleep habits, and growth rates in body weight and length throughout the study. However, compared to the control group, infants in the investigational and human milk groups had significantly: (i) greater body length at 90, 120, and 150 days of age; (ii) greater growth rate in head circumference from 30 to 60 days of age, with larger head circumference at 60 days of age; (iii) larger daily stool frequency at 60, 90, and 120 days of age; (iv) softer stool at 60, 90, and 120 days of age; (v) higher bone quality index and bone speed of sound at 150 days of age; (vi) fewer hours of crying at 60 and 90 days of age; (vii) less abdominal distention, burp, and flatus at 60, 90, and 120 days of age; and (viii) less constipation at 90 days of age. At other time points, no significant differences were observed between the three groups. No serious adverse events (AEs) related to the study products were reported, and significantly fewer infants in the investigational and HM groups experienced at least one AE compared to the control group. The study suggests that the A2 β-casein formula with high sn-2 palmitate and CPP supports adequate growth, is well tolerated, and may have beneficial effects on stool consistency, gastrointestinal comfort, crying duration, and bone density, comparable to HM.

Clinical trial registration:https://clinicaltrials.gov/, NCT04749290.
A dual-radiomics model for overall survival prediction in early-stage NSCLC patient using pre-treatment CT images
Authors: Zhang Rihui , Zhu Haiming , Chen Minbin , Sang Weiwei , Lu Ke , Li Zhen , Wang Chunhao , Zhang Lei , Yin Fang-Fang , Yang Zhenyu
Published: August 2024

Introduction

Radiation therapy (RT) is one of the primary treatment options for early-stage non-small cell lung cancer (ES-NSCLC). Therefore, accurately predicting the overall survival (OS) rate following radiotherapy is crucial for implementing personalized treatment strategies. This work aims to develop a dual-radiomics (DR) model to (1) predict 3-year OS in ES-NSCLC patients receiving RT using pre-treatment CT images, and (2) provide explanations between feature importanceand model prediction performance.

Methods

The publicly available TCIA Lung1 dataset with 132 ES-NSCLC patients received RT were studied: 89/43 patients in the under/over 3-year OS group. For each patient, two types of radiomic features were examined: 56 handcrafted radiomic features (HRFs) extracted within gross tumor volume, and 512 image deep features (IDFs) extracted using a pre-trained U-Net encoder. They were combined as inputs to an explainable boosting machine (EBM) model for OS prediction. The EBM’s mean absolute scores for HRFs and IDFs were used as feature importance explanations. To evaluate identified feature importance, the DR model was compared with EBM using either (1) key or (2) non-key feature type only. Comparison studies with other models, including supporting vector machine (SVM) and random forest (RF), were also included. The performance was evaluated by the area under the receiver operating characteristic curve (AUCROC), accuracy, sensitivity, and specificity with a 100-fold Monte Carlo cross-validation.

Results

The DR model showed highestperformance in predicting 3-year OS (AUCROC=0.81 ± 0.04), and EBM scores suggested that IDFs showed significantly greater importance (normalized mean score=0.0019) than HRFs (score=0.0008). The comparison studies showed that EBM with key feature type (IDFs-only demonstrated comparable AUCROC results (0.81 ± 0.04), while EBM with non-key feature type (HRFs-only) showed limited AUCROC (0.64 ± 0.10). The results suggested that feature importance score identified by EBM is highly correlated with OS prediction performance. Both SVM and RF models were unable to explain key feature type while showing limited overall AUCROC=0.66 ± 0.07 and 0.77 ± 0.06, respectively. Accuracy, sensitivity, and specificity showed a similar trend.

Discussion

In conclusion, a DR model was successfully developed to predict ES-NSCLC OS based on pre-treatment CT images. The results suggested that the feature importance from DR model is highly correlated to the model prediction power.
Contrast-enhanced computed tomography-based radiomics nomogram for predicting HER2 status in urothelial bladder carcinoma
Authors: Peng Jiao , Tang Zhen , Li Tao , Pan Xiaoyu , Feng Lijuan , Long Liling
Published: August 2024

Objective

To evaluate the performance of a clinical-radiomics model based on contrast-enhanced computed tomography (CE-CT) in assessing human epidermal growth factor receptor 2 (HER2) status in urothelial bladder carcinoma (UBC).

Methods

From January 2022 to December 2023, 124 patients with UBC were classified into the training (n=100) and test (n=24) sets. CE-CT scans were performed on the patients. Univariate and multivariate analyses were conducted to identify independent predictors of HER2 status in patients with UBC. We employed eight machine learning algorithms to establish radiomic models. A clinical-radiomics model was developed by integrating radiomic signatures and clinical features. Receiver operating characteristic curves and decision curve analysis (DCA) were generated to evaluate and validate the predictive capabilities of the models.

Results

Among the eight classifiers, the random forest radiomics model based on CE-CT demonstrated the highest efficacy in predicting HER2 status, with area under the curve (AUC) values of 0.880 (95% CI: 0.813–0.946) and 0.814 (95% CI: 0.642–0.986) in the training and test sets, respectively. In the training set, the clinical-radiomics model achieved an AUC of 0.935, an accuracy of 0.870, a sensitivity of 0.881, and a specificity of 0.854. In the test set, the clinical-radiomics model achieved an AUC of 0.857, an accuracy of 0.760, a sensitivity of 0.643, and a specificity of 0.900. DCA analysis indicated that the clinical-radiomics model provided good clinical benefit.

Conclusion

The radiomics nomogram demonstrates good diagnostic performance in predicting HER2 expression in patients with UBC.
Analysis of the causes of neonatal death and genetic variations in congenital anomalies: a multi-center study
Authors: Yang Xue , Bai Ruimiao , Zhang Juan , Yang Yunfan , Zhang JuanJuan , Wang Baozhu , Li Zhankui , Yu Xiping
Published: August 2024

Background

Neonatal deaths often result from preventable conditions that can be addressed with appropriate interventions. This study aims to analyze the distribution of the causes of neonatal death and explore genetic variations that lead to congenital anomalies in Northwest China.

Methods

This multi-center observational study was conducted across six medical centers in Shaanxi province, Northwest China. Clinical data were retrospectively collected from neonates admitted between 2016 and 2020. Kaplan-Meier analysis was utilized to estimate survival rates, while high-throughput sequencing platforms were employed to detect mutations causing congenital anomalies.

Results

Among 73,967 neonates requiring hospital care, 424 neonatal deaths were recorded, leading to a neonatal mortality rate of 0.57%. The primary causes of death included neonatal respiratory distress syndrome (23.8%), birth asphyxia (19.8%), neonatal septicemia (19.3%), and congenital anomalies (13.6%). The leading causes of neonatal deaths due to congenital anomalies were congenital heart defects (38.6%), bronchopulmonary dysplasia (14.0%), and inherited metabolic disorders (10.5%). Genetic analysis identified 83 pathogenic or likely pathogenic variants in 23 genes among the neonates with congenital anomalies, including four novel mutations (c.4198+1G>T, c.1075delG, c.610-1G>A, c.7769C>T) in the ABCC8, CDKL5, PLA2G6, and NIPBL genes.

Conclusion

Congenital anomalies represent a significant and preventable cause of neonatal deaths in Northwest China. Early detection of congenital anomalies through genetic testing and comprehensive prenatal care are crucial for reducing neonatal mortality rates and improving pregnancy outcomes.
Ling-gui-zhu-gan promotes adipocytes browning via targeting the miR-27b/PRDM16 pathway in 3T3-L1 cells
Authors: Ye Zimengwei , Zhao Yi , Cui Yanjing , Xu Bingrui , Wang Fan , Zhao Dandan , Dong Guangtong , Wang Zhufeng , Wu Rui
Published: August 2024

Introduction: Obesity, a global epidemic, is caused by an imbalance between energy intake and expenditure. The induction of white adipose browning to increase heat production has emerged as a potential effective strategy to address obesity. Ling-gui-zhu-gan (LGZG), a traditional Chinese medicine formula, has been proved to achieve promising results to combat obesity and related metabolic diseases, yet the mechanisms remain largely unexplored. This study aimed to elucidate the anti-obesity properties and the mechanisms of LGZG by investigating its browning effect on 3T3-L1 adipocytes.

Methods: LGZG-containing serum obtained by oral administration of LGZG to animals was added to 3T3-L1 adipocytes to simulate in vivo conditions.

Results: The results showed that 49 compounds were identified in LGZG-containing serum by UHPLC-Q-Orbitrap HRMS, including compounds such as atractylenolides and polyporenic acid C, etc. LGZG-containing serum alleviated the lipid accumulation and decreased both intracellular and extracellular triglyceride contents in a dose-dependent manner. This reduction is accompanied by enhanced mitochondrial respiratory and heat production function. Mechanistically, LGZG-containing serum led to a decrease in miR-27b expression and an increase in the mRNA and protein levels of browning-related markers, including UCP1, PRDM16, PGC-1α, PPARγ, CTBP1, and CTBP2. Further investigation using miR-27b mimic transfection confirmed that miR-27b/PRDM16 pathway might be a potential mechanism by which LGZG-containing serum promotes browning of 3T3-L1 adipocytes.

Discussion: These results underscore the therapeutic potential of LGZG in addressing obesity and its associated metabolic disorders through the promotion of adipose browning.
Cost-effectiveness of pembrolizumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced biliary tract cancer in China and the US
Authors: Luo Xianmei , Cai Tingting , Wu Jinyan , Li Xingyu , Wang Xiaofan , Ma Haiying
Published: August 2024

Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US).

Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model’s robustness was analyzed through one-way sensitivity analysis and probabilistic sensitivity analysis.

Results: Basic data analysis illustrates that pembrolizumab ($2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $38,201.19 in China, and the additional cost relative to chemotherapy regimens was $77,114.94 (ICER $556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ($54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $229,044, and the total cost increased by $160,425.24 (ICER $1,109,462.92/QALY).

Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a cost-effective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices.
CYP2D6 copy number determination using digital PCR
Authors: Wang Wendy Y. , Lin Lancy , Boone Erin C. , Stevens Junko , Gaedigk Andrea
Published: August 2024

Background

CYP2D6 testing is increasingly used to guide drug therapy and thus, reliable methods are needed to test this complex and polymorphic gene locus. A particular challenge arises from the detection and interpretation of structural variants (SVs) including gene deletions, duplications, and hybrids with the CYP2D7 pseudogene. This study validated the Absolute Q™ platform for digital PCR-based CYP2D6 copy number variation (CNV) determination by comparing results to those obtained with a previously established method using the QX200 platform. In addition, protocols for streamlining CYP2D6 CNV testing were established and validated including the “One-pot” single-step restriction enzyme digestion and a multiplex assay simultaneously targeting the CYP2D6 5′UTR, intron 6, and exon 9 regions.

Methods

Genomic DNA (gDNA) samples from Coriell (n = 13) and from blood, saliva, and liver tissue (n = 17) representing 0–6 copies were tested on the Absolute Q and QX200 platforms. Custom TaqMan™ copy number (CN) assays targeting CYP2D6 the 5′UTR, intron 6, and exon 9 regions and a reference gene assay (TERT or RNaseP) were combined for multiplexing by optical channel. In addition, two digestion methods (One-pot digestion and traditional) were assessed. Inconclusive CN values on the Absolute Q were resolved using an alternate reference gene and/or diluting gDNA.

Results

Overall, results between the two platforms and digestions methods were consistent. The “One-pot” digestion method and optically multiplexing up to three CYP2D6 regions yielded consistent result across DNA sample types and diverse SVs, reliably detecting up to 6 gene copies. Rare variation in reference genes were found to interfere with results and interpretation, which were resolved by using a different reference.

Conclusion

The Absolute Q produced accurate and reliable CYP2D6 copy number results allowing for a streamlined and economical protocol using One-pot digestion and multiplexing three target regions. Protocols are currently being expanded to other pharmacogenes presenting with SVs/CNVs.
Safeguarding migrant and refugee children: a critical contemporary challenge
Authors: Gerson Diana , Al Marzooqi Dana Humaid , Argyriades Demetrios
Published: August 2024

This paper investigates the pivotal role of psycho-social support in bolstering the mental and spiritual well-being of migrant and refugee children. It highlights the necessity to shield these vulnerable groups from spiritual abuse within humanitarian efforts. Remarkably, an estimated 117 million people are currently displaced by conflict, violence, war, and natural disasters, and as of 2023, nearly half of them are under the age of 18. The call, therefore, for culturally sensitive, effective interventions is manifestly urgent. Our research underscores, in order to highlight, the significance of professionalizing faith-based and local faith actors to advocate for standards that mitigate the risks of religious exploitation and safeguard the children’s spiritual identity, practices, and beliefs. We highlight the existing gaps in the literature and propose a framework for further research. Our focus is on the effectiveness of the Global Compact on Refugees and the impact of local versus global policies on the protection and well-being of migrant and refugee children. Our analysis extends to humanitarian agencies’ and caregivers’ best practices and prevention strategies. It further emphasizes the importance of safeguarding neutrality at all times and promoting community reintegration. Our findings call for a concerted effort to enhance professionalism among those working with refugees in humanitarian frameworks, prioritizing children’s spiritual, mental, and physical well-being. This study seeks to contribute to the ongoing discourse on the rights of children on the move. It advocates for policies and practices that recognize their vulnerability and potential for resilience.