bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent modulation of activated protein C pleiotropic functions by antibodies that differ by a single amino acid
Authors: Sim Derek S. , Shukla Meenal , Mallari Cornell R. , Fernández José A. , Xu Xiao , Schneider Doug , Bauzon Maxine , Hermiston Terry W. , Mosnier Laurent O.
Published: October 2024

Activated protein C (APC) is a pleiotropic plasma protease with diverse functions derived from its anticoagulant, anti-inflammatory, and cytoprotective activities. The selective uncoupling and/or modulation of these APC activities by antibodies may have therapeutic benefit in diseases such as traumatic bleeding, hemophilia, sepsis, and ischemia. TPP-26870 is an antibody that targets a nonactive site of APC for the selective modulation of APC activities. To optimize the potency of TPP-26870, variants with single amino acid mutation in the complementarity-determining regions (CDRs) were screened, and 21 variants with improved affinity constant were identified. Interestingly, the affinity maturation of TPP-26870 did not merely generate a panel of variants with higher potency in functional assays. Functional data demonstrated that the pleiotropic functions of APC were very sensitive to epitope-CDR interactions. Single amino acid mutations within the CDRs of TPP-26870 were sufficient to elicit divergent antagonistic and agonistic effects on the various APC functional activities. These include prolonged in vitro APC plasma half-life, increased inhibition of anticoagulant activity, and agonistic enhancement of histone H3 cleavage, while having less impact on protease-activated receptor 1 cleavage, compared with TPP-26870. This study illustrates that APC is highly sensitive to non–active site targeting that can lead to unpredictable changes in its activity profile of this pleiotropic enzyme. Furthermore, this study demonstrates the ability to modify APC functions to advance the potential development of APC-targeted antibodies as therapeutics for the treatment of diseases including trauma bleeding, hemophilia, ischemia, and sepsis.
Hematopoietic cell transplant compared with standard care in adolescents and young adults with sickle cell disease
Authors: Walters Mark C. , Eapen Mary , Liu Yiwen , El Rassi Fuad , Waller Edmund K. , Levine John E. , Strouse John J. , Antin Joseph H. , Parikh Suhag H. , Bakshi Nitya , Dampier Carlton , Jaroscak Jennifer J. , Bergmann Shayla , Wong Trisha , Kota Vamsi , Pace Betty , Lekakis Lazaros J. , Lulla Premal , Nickel Robert S. , Kasow Kimberly A. , Popat Uday , Smith Wally , Yu Lolie , DiFronzo Nancy , Geller Nancy , Kamani Naynesh , Klings Elizabeth S. , Hassell Kathryn , Mendizabal Adam , Sullivan Keith , Neuberg Donna , Krishnamurti Lakshmanan
Published: October 2024

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives were a comparison of the changes in SCD-related events, functional outcomes, and organ function. The data were analyzed according to the intent-to-treat principle. A total of 113 participants were enrolled with 28 in the donor arm and 85 in the no donor arm. The 2-year probabilities of survival were 89% and 93%, in the donor vs no donor arms. Vaso-occlusive pain (VOC) was less frequent in the donor arm in the second year after biologic assignment (P < .001). Based on PROMIS-57 surveys, there was a decrease in fatigue (P = .003) and an increase in the ability to participate in social roles and activities (P = .003) in the donor arm 2 years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the donor arm led to improvements in VOC, fatigue, and social function. This trial was registered at www.clinicaltrials.gov as #NCT02766465.
Experimental study on seismic performance of glulam structural columns with anchored connections
Authors: Li Xiaowei , Liu Jihang , Zhang Zhaoqiang , Ma Dongwen , Pang Lidan
Published: October 2024

In current timber structures, the low initial stiffness, and weak bending resistance of the connections result in significant structural deformation and failures. To improve the mechanical capabilities of timber structural joints, a novel timber-component anchorage system with robust bending resistance was introduced. Thirteen scaled-down specimens of glulam columns with anchored connections were meticulously fabricated for testing, scaled at a ratio of 1/2. Cyclic loading tests were conducted, considering three types of the volume compression percentage of confined wood perpendicular to the grain; and five axial-load levels. Subsequently, various seismic performance aspects of glulam columns with anchored connections were examined, including the failure mode, hysteresis behavior, envelope curve, strength degradation, stiffness degradation, energy dissipation capacity, and critical points. During the analysis, the influence of the P–Δ effect on the results was discussed and a damage-based hysteretic model was presented. Finally, a comparison of the mechanical performance for various types of timber structural joints was conducted. The findings revealed that the failure mode of the anchored glulam columns occurred as cracking perpendicular to the grain, and the anchored columns exhibited superior bending resistance and overall seismic performance.
Fiber morphological characteristics of bamboo Ferrocalamus strictus culms from different geographical distribution regions
Authors: Zheng Xiaofeng , Xu Rui , He Honglan , Wang Jiamin , Zhou Ziten , Zhan Hui , Wang Yingqiong , Deng Jiayi , Wang Changming
Published: October 2024

The fiber index including fiber length, width, wall thickness and lumen diameter of Ferrocalamus strictus culms (1, 2, and ≥ 3 years) from Jinping, Mojiang and Lvchun counties of Yunnan Province was determined and the elemental content of the soil was also determined to analyze the fiber characteristics. The average relative fiber index measured for F. strictus culms were fiber length (1.30 mm), width (21.57 μm), slenderness ratio (60.79 μm), wall thickness (4.21 μm), lumen diameter (7.22 μm), and runkel ratio (1.22 μm), which belonged to the range of middle and long fibers. The fiber length increased with the culm age. The proportion of long fiber increased while short fibers decreased along with culm maturing. The fiber morphology did not show a specific trend with the culm height. Fiber length reached the maximum in the bottom portions of the culms. There is a correlation between fiber morphology and soil elements, the content of organic matter, total potassium, total sulfur, total aluminum, total zinc, total iron, total boron, alkali-hydrolyzed nitrogen and available silicon in the soil affects fiber morphology. The content of organic matter, total boron and alkali-hydrolyzed nitrogen in the soil from Mojiang County was largest. Comparatively, the culm fiber in Mojiang County had the best fiber index performance for utilization, since the greatest proportion of medium and long fibers and the optimal distribution of fiber length frequency was obtained from the culms in Mojiang County. This study can provide a theoretical basis for large-scale bamboo forest cultivation and the development and utilization of bamboo culm fiber.
Validation of CASPRI, GO-FAR, PIHCA scores in predicting favorable neurological outcomes after in-hospital cardiac arrest; A five-year three center retrospective study in IRAN
Authors: Alamuti Fatemeh safari , Hosseinigolafshani Seyedehzahra , Ranjbaran Mehdi , Yekefallah Leili
Published: October 2024

Background

Predicting neurological outcomes following in-hospital cardiac arrest is crucial for guiding subsequent clinical treatments. This study seeks to validate the effectiveness of the CASPRI, GO-FAR, and PIHCA tools in predicting favorable neurological outcomes after in-hospital cardiac arrest.

Method

This retrospective study utilized a Utstein-style structured form to review the medical records of patients who experienced in-hospital cardiac arrest between March 2018 and March 2023. Predictors were examined using multivariable logistic regression, and the validity of the tools was assessed using ROC curves. Statistical analysis was conducted using SPSS version 25 software.

Results

Out of the 1100 patients included in the study, 42 individuals (3.8%) achieved a favorable neurological outcome. multivariable regression analysis revealed that age, respiratory failure, resuscitation shift, duration of renal failure, and CPC score 24 h before cardiac arrest were significantly associated with favorable neurological outcomes. The predictive abilities of the CASPRI, GO-FAR, and PIHCA scores were calculated as 0.99 (95% CI, 0.98–1.00), 0.98 (95% CI, 0.97–0.99), and 0.96 (95% CI, 0.94–0.99) respectively. A statistically significant difference was observed in the predictive abilities of the CASPRI and PIHCA scores (P = 0.001), while the difference between CASPRI and GO-FAR did not reach significance (P = 0.057). Additionally, there was no significant difference between the predictive abilities of GO-FAR and PIHCA scores (P = 0.159).

Conclusion

The study concludes that CASPRI and GO-FAR scores show strong potential as objective measures for predicting favorable neurological outcomes post-cardiac arrest. Integrating these scores into clinical decision-making may enhance treatment and care strategies, in the Iranian healthcare context.
A clinical trial of ropivacaine in arthocentesis for TMD
Authors: Huang Laifeng , Huang Zeliu , Bi Shiyun , Mai Huaming
Published: October 2024

Introduction

This study aims to compare the efficacy of ropivacaine and lidocaine in the treatment of temporomandibular joint (TMJ) disorders, with the goal of exploring a more effective treatment for TMJ disorders.

Methods

Patients with Wilkes stage III and IV unilateral TMJ disorders were enrolled in the study. 0.5% ropivacaine was used for local anesthesia in group A, 2% lidocaine was used in group B. Sodium hyaluronate was injected after supra-articular lavage in both groups. The patients’ general conditions, pain scores, and maximum opening before and after treatment were collected, the time of onset and maintenance of anesthesia, and the levels of inflammatory factors IL-1β and IL-6 in the joint lavage fluid were detected.

Results

Study showed that the onset of anesthesia was faster and longer maintained in group A. The decrease in IL-1β was more pronounced in group A (16.08 ± 3.10) than in group B (18.03 ± 2.84), p < 0.05. At 2 months after treatment, the joint clicking rate was higher in group A (75%) compared to group B (35%), p < 0.05. At 3 months after treatment, the joint clicking rate was higher in group A (76.69%) compared to group B (40%) and the maximum mouth opening was greater in group A (45.00 ± 2.38) compared to group B (41.73 ± 4.18), p < 0.05. There were no statistically significant differences in VAS score and lateral excursion in group A compared with group B at 2 months and 3 months after treatment.

Conclusions

Compared with lidocaine, the application of ropivacaine combined with sodium hyaluronate supra-articular lavage for the treatment of temporomandibular joint disorder is more clinically effective.

Clinical trials Registration Number

ChiCTR2300075241 (30/08/2023).
An item bank to measure health-related quality of life among young children (0-5-years-old) affected by respiratory illnesses – expert stakeholders and end-users from the Western Cape, South Africa
Authors: Anthony Michaile Gizelle , Van Niekerk Margaret , Hesseling Anneke Catharina , Hoddinott Graeme , van der Zalm Marieke Margreet
Published: October 2024

Background

Health-related quality of life (HRQoL) is a crucial patient-centred outcome for developing policy. However, there is a lack of appropriate HRQoL measures for young children (0-5-years), who are particularly vulnerable to respiratory illnesses like pulmonary tuberculosis (PTB) and other respiratory infections, especially in low- and middle-income countries (LMICs). We aimed to develop a disease-specific HRQoL item bank for young children with acute and chronic respiratory illnesses.

Methods

An exploratory sequential design with three phases was used to develop a HRQoL item bank. The content validity of the item bank was evaluated by local and international experts specialising in HRQoL and child health. The group included paediatric pulmonologists, researchers with expertise in respiratory illnesses, and experts in scale development. Cognitive interviews with 37 caregivers of children with TB, pneumonia, adenovirus respiratory infection, other lower respiratory tract infections, reactive airway disease, and protracted bronchitis in Cape Town, South Africa, and consultations with 22 stakeholders were conducted for final revisions. The item bank was progressively refined at each phase of the study.

Findings

The Delphi experts recommended dividing the item bank into two age groups (0-2-years and 3-5-years) and using a 5-point Likert scale. Overall, 41 items (42%) met the predetermined > 70% threshold for inclusion in the item bank. Cognitive interviews confirmed that the domains were relevant. Minor modifications were made to five items in cohort 1 (0-2-years) and seven in cohort 2 (3-5-years), with 8 items (13%) and 14 items (22%) excluded. Phase 3 consultations emphasised the importance of including all seven domains and expanding the items to cover early childhood development, play, social interactions, and care routines. The final item bank includes versions for both age groups and incorporates these refinements.

Conclusion

An item bank was developed as a first step to develop a comprehensive disease-specific HRQoL tool for young children with respiratory illnesses in an LMIC. Input from caregivers and content experts was crucial in creating two HRQoL item banks tailored to the developmental differences between 0 and 2 and 3-5-year age groups. Their contributions ensured the tool effectively captures age-appropriate aspects of HRQoL. Future studies should focus on assessing the validity and reliability of these item banks.
Outcomes of odontoid fractures with associated cardiac arrest: retrospective bi-center case series and systematic literature review
Authors: Schaible S. F. , Häckel S. , Rutsch N. , Aregger F. C. , Bigdon S. F. , Schoenborn V. , Broger I. , Albers C. E. , Tinner C.
Published: October 2024

Background

Odontoid fractures from high-energy trauma are associated with significant morbidity and mortality, including spinal cord injury, neurological damage, and cardiac arrest. The literature on odontoid fractures leading to cardiac arrest is limited to isolated case reports. This study aims to conduct a retrospective bi-center case series and a systematic review of existing literature.

Methods

We conducted a retrospective bi-center case series on patients with odontoid fractures from high-energy trauma who experienced post-traumatic cardiac arrest with return of spontaneous circulation (ROSC) after CPR from two Level 1 Trauma Centers (2008–2024). The primary outcome was in-hospital mortality; secondary outcomes included epidemiological, pre-hospital, and in-hospital data, and CT and MRI findings. Additionally, we performed a systematic literature review to summarize existing evidence.

Results

The study included 25 patients (mean age 71.1 ± 12.3 years, SD; 8 females). The mortality rate was 92% (23 patients). Median downtime before CPR was 5.0 min (IQR: 7.0), with CPR lasting 17.0 min (IQR: 13.0), primarily initiated by professionals (60%). All patients were quadriplegic. Type II Anderson d’Alonzo fractures were most common (88%), with all patients showing myelopathy on MRI. Only three patients (12%) underwent surgical intervention due to favorable prognosis. Our literature review identified seven case reports, with two patients surviving and one achieving full recovery.

Conclusions

In this case series, patients experiencing cardiac arrest after odontoid fractures exhibited high mortality rates despite comprehensive management at Level 1 trauma centers. Survivors faced significant and enduring morbidity.
Neglecting the impact of normalization in semi-synthetic RNA-seq data simulations generates artificial false positives
Authors: Hejblum Boris P. , Ba Kalidou , Thiébaut Rodolphe , Agniel Denis
Published: October 2024

A recent study reported exaggerated false positives by popular differential expression methods when analyzing large population samples. We reproduce the differential expression analysis simulation results and identify a caveat in the data generation process. Data not truly generated under the null hypothesis led to incorrect comparisons of benchmark methods. We provide corrected simulation results that demonstrate the good performance of dearseq and argue against the superiority of the Wilcoxon rank-sum test as suggested in the previous study.
Effects of the informed health choices secondary school intervention after 1 year: a prospective meta-analysis using individual participant data
Authors: Chesire Faith , Mugisha Michael , Ssenyonga Ronald , Rose Christopher J. , Nsangi Allen , Kaseje Margaret , Sewankambo Nelson K. , Oxman Matt , Rosenbaum Sarah E. , Moberg Jenny , Dahlgren Astrid , Lewin Simon , Venkateswaran Mahima , Papadopoulou Eleni , Oxman Andrew D.
Published: October 2024

Background

Critical thinking about health choices is essential to avoid being misled by unreliable information and to use reliable information appropriately. The aim of this prospective meta-analysis was to synthesize the results of 1-year follow-up data from three cluster-randomized trials of an intervention designed to teach lower secondary school students to think critically about health choices. Only one other randomized trial has evaluated a school-based intervention to teach adolescents to think critically about health choices. That trial compared two teaching strategies to teach statistical reasoning. It did not assess long-term learning-retention.

Methods

We conducted the trials in Kenya, Rwanda, and Uganda. The intervention included providing a 2–3-day teacher training workshop and digital resources for ten lessons. The intervention focused on nine key concepts. We did not intervene in control schools. The primary outcome was a passing score on a test (≥ 9 of 18 multiple-choice questions answered correctly). We performed random effects meta-analyses to estimate the overall intervention effects. We calculated learning retention as the test results in the intervention schools after 1 year relative to just after the intervention, adjusted for chance.

Results

Altogether, 244 schools (11,344 students) took part in the three trials. Follow-up data was collected for 8298 students (73%). The overall odds ratio for the primary outcome after 1 year was 3.6 (95% CI: 1.9–7.1;p = 0.0001) in favor of the intervention, whereas it was 5.5 (95% CI: 3.0–10.2) just after the intervention. This corresponds to 25.6% (95% CI: 21.1–30.0%) more students in the intervention schools passing the test after 1 year versus 33.3% (95% CI: 28.7–37.8%) just after the intervention. Overall, 2273 (52.6%) of 4324 students in intervention schools had a passing score after 1 year compared to 3397 (58.1%) of 5846 students just after the intervention, indicating 88.3% learning retention.

Conclusions

One year after the intervention, we still found a positive effect on the ability of students to think critically about health choices, but 5.5% fewer students in the intervention schools had a passing score. The certainty of the evidence was also lower due to 27% of students being lost to follow-up.

Trial registration

The protocol for this prospective meta-analysis was registered with PROSPERO May 31, 2022, ID 336580. The three randomized trials were registered in the Pan African Clinical Trial Registry February 15, 2022, PACTR202203880375077; April 5, 2022, PACTR20220488391731; and April 14, 2022, PACTR202204861458660.
Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery
Authors: Josephs Katherine S. , Seaby Eleanor G. , May Philippa , Theotokis Pantazis , Yu Jing , Andreou Avgi , Sinclair Hannah , Morris-Rosendahl Deborah , Thomas Ellen R. A. , Ennis Sarah , Roberts Angharad M. , Ware James S.
Published: October 2024

Background

Cardiomyopathies are clinically important conditions, with a strong genetic component. National genomic initiatives such as 100,000 Genome Project (100KGP) provide opportunity to study these rare conditions at scale beyond conventional research studies.

Methods

We present the clinical and molecular characteristics of the 100KGP cohort, comparing paediatric and adult probands with diverse cardiomyopathies. We assessed the diagnostic yield and spectrum of genetic aetiologies across clinical presentations. We re-analysed existing genomic data using an updated analytical strategy (revised gene panels; unbiased analyses of de novo variants; and improved variant prioritisation strategies) to identify new causative variants in genetically unsolved children.

Results

We identified 1918 individuals (1563 probands, 355 relatives) with cardiomyopathy (CM) in 100KGP. Probands, comprising 273 children and 1290 adults, were enrolled under > 55 different recruitment categories. Paediatric probands had higher rates of co-existing congenital heart disease (12%) compared to adults (0.9%). Diagnostic yield following 100KGP’s initial analysis was significantly higher for children (19%) than for adults (11%) with 11% of diagnoses overall made in genes not on the existing UK paediatric or syndromic CM panel. Our re-analysis of paediatric probands yields a potential diagnosis in 40%, identifying new probable or possible diagnoses in 49 previously unsolved paediatric cases. Structural and intronic variants accounted for 11% of all potential diagnoses in children while de novo variants were identified in 17%.

Conclusions

100KGP demonstrates the benefit of genome sequencing over a standalone panel in CM. Re-analysis of paediatric CM probands allowed a significant uplift in diagnostic yield, emphasising the importance of iterative re-evaluation in genomic studies. Despite these efforts, many children with CM remain without a genetic diagnosis, highlighting the need for better gene-disease relationship curation and ongoing data sharing. The 100KGP CM cohort is likely to be useful for further gene discovery, but heterogeneous ascertainment and key technical limitations must be understood and addressed.
Population structure of Desmophyllum pertusum found along the United States eastern continental margin
Authors: Weinnig Alexis M. , Aunins Aaron W. , Salamone Veronica , Quattrini Andrea M. , Nizinski Martha S. , Morrison Cheryl L.
Published: October 2024

Objective

The connectivity and genetic structuring of populations throughout a region influence a species’ resilience and probability of recovery from anthropogenic impacts. By gaining a comprehensive understanding of population connectivity, more effective management can be prioritized. To assess the connectivity and population genetic structure of a common cold-water coral species, Desmophyllum pertusum (Lophelia pertusa), we performed Restriction-site Associated DNA Sequencing (RADseq) on individuals from nine sites ranging from submarine canyons off New England to the southeastern coast of the United States (SEUS) and the Gulf of Mexico (GOM). Fifty-seven individuals and 3,180 single-nucleotide polymorphisms (SNPs) were used to assess genetic differentiation.

Results

High connectivity exists among populations along the SEUS, yet these populations were differentiated from those to the north off New England and in Norfolk Canyon along the North Atlantic coast of the United States, as well as those in the GOM. Interestingly, Norfolk Canyon, located just north of North Carolina, and GOM populations exhibited low levels of genetic differentiation, corroborating previous microsatellite analyses and signifying gene flow between these populations. Increasing sample sizes from existing populations and including additional sampling sites over a larger geographic range would help define potential source populations and reveal fine-scale connectivity patterns among D. pertusum populations.
Human mesenchymal stem/stromal cell based-therapy in diabetes mellitus: experimental and clinical perspectives
Authors: Zeinhom Alaa , Fadallah Sahar A. , Mahmoud Marwa
Published: October 2024

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant global health challenge, with current treatments often fail to prevent the long-term disease complications. Mesenchymal stem/stromal cells (MSCs) are, adult progenitors, able to repair injured tissues, exhibiting regenerative effects and immunoregulatory and anti-inflammatory responses, so they have been emerged as a promising therapeutic approach in many immune-related and inflammatory diseases. This review summarizes the therapeutic mechanisms and outcomes of MSCs, derived from different human tissue sources (hMSCs), in the context of DM type 1 and type 2. Animal model studies and clinical trials indicate that hMSCs can facilitate pleiotropic actions in the diabetic milieu for improved metabolic indices. In addition to modulating abnormally active immune system, hMSCs can ameliorate peripheral insulin resistance, halt beta-cell destruction, preserve residual beta-cell mass, promote beta-cell regeneration and insulin production, support islet grafts, and correct lipid metabolism. Moreover, hMSC-free derivatives, importantly extracellular vesicles, have shown potent experimental anti-diabetic efficacy. Moreover, the review discusses the diverse priming strategies that are introduced to enhance the preclinical anti-diabetic actions of hMSCs. Such strategies are recommended to restore the characteristics and functions of MSCs isolated from patients with DM for autologous implications. Finally, limitations and merits for the wide spread clinical applications of MSCs in DM such as the challenge of autologous versus allogeneic MSCs, the optimal MSC tissue source and administration route, the necessity of larger clinical trials for longer evaluation duration to assess safety concerns, are briefly presented.

Graphical Abstract
Human-specific protein-coding and lncRNA genes cast sex-biased genes in the brain and their relationships with brain diseases
Authors: He Sha , Zhang Xuecong , Zhu Hao
Published: October 2024

Background

Gene expression shows sex bias in the brain as it does in other organs. Since female and male humans exhibit noticeable differences in emotions, logical thinking, movement, spatial orientation, and even the incidence of neurological disorders, sex biases in the brain are especially interesting, but how they are determined, whether they are conserved or lineage specific, and what the consequences of the biases are, remain poorly explored and understood.

Methods

Based on RNA-seq datasets from 16  and 14 brain regions in humans and macaques across developmental periods and from patients with brain diseases, we used linear mixed models (LMMs) to differentiate variations in gene expression caused by factors of interest and confounding factors and identify four types of sex-biased genes. Effect size and confidence in each effect were measured upon the local false sign rate (LFSR). We utilized the biomaRt R package to acquire orthologous genes in humans and macaques from the BioMart Ensembl website. Transcriptional regulation of sex-biased genes by sex hormones and lncRNAs were analyzed using the CellOracle, GENIE3, and Longtarget programs. Sex-biased genes’ functions were revealed by gene set enrichment analysis using multiple methods.

Results

Lineage-specific sex-biased genes greatly determine the distinct sex biases in human and macaque brains. In humans, those encoding proteins contribute directly to immune-related functions, and those encoding lncRNAs intensively regulate the expression of other sex-biased genes, especially genes with immune-related functions. The identified sex-specific differentially expressed genes (ssDEGs) upon gene expression in disease and normal samples also indicate that protein-coding ssDEGs are conserved in humans and macaques but that lncRNA ssDEGs are not conserved. The results answer the above questions, reveal an intrinsic relationship between sex biases in the brain and sex-biased susceptibility to brain diseases, and will help researchers investigate human- and sex-specific ncRNA targets for brain diseases.

Conclusions

Human-specific genes greatly cast sex-biased genes in the brain and their relationships with brain diseases, with protein-coding genes contributing to immune response related functions and lncRNA genes critically regulating sex-biased genes. The high proportions of lineage-specific lncRNAs in mammalian genomes indicate that sex biases may have evolved rapidly in not only the brain but also other organs.
Solar cycle phase and occurrence of intense geomagnetic storms
Authors: Watari S.
Published: October 2024

Solar cycles have an asymmetrical shape with a fast rise and a slow decline, which varies from cycle to cycle. This makes it difficult to study the solar cycle phase dependence of the occurrence of intense solar-terrestrial events such as intense geomagnetic storms. In the previous works, differences in the rise and fall time lengths of each solar cycle were not fully considered. We normalized the asymmetric shape of each solar cycle using the rise and fall time lengths and showed the solar cycle phase dependence of occurrence of the intense geomagnetic storms selected using the Dst index for solar cycles 19−24 and using the aa index for solar cycles 12−24. The previous works noted that the occurrence of geomagnetic disturbances shows double peaks before and after solar maximum. Our results showed that the occurrence of the intense geomagnetic storms selected using the Dst and aa indices does not always show clear double peaks and increased more in the earlier half of the fall time than in the other time periods. The Dst and aa indices have been used to select geomagnetic storms in the previous studies. We pointed out that the solar cycle phase dependence of occurrence of the geomagnetic storms selected using the aa index is slightly different from those selected using the Dst index. We showed the geomagnetic storm on 4 August 1972 as an extreme case, which showed difference between Dst and aa. We also showed that intense geomagnetic storms associated with eruptive flares from the active sunspot groups occurred around the solar minima of cycles 17, 19, 20, and 21.

Graphical Abstract
Dietary practices and associated factors among adult diabetic patients at academic tertiary-level hospitals in central Ethiopia: convergent mixed study
Authors: Saliya Sentayehu Admasu , Ashine Taye Mezgebu , Heliso Asnakech Zekiwos , Babore Getachew Ossabo , Birhanu Bethelhem , Hailu Awoke Girma , Sebro Sisay Foga , Ezo Elias , Begizew Selamawit Wondale
Published: October 2024

Background

Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide. Despite the existence of national strategies to prevent potential complications, DM-related morbidities and mortality continue to rise in Ethiopia. Although studies have been conducted regarding dietary practices among DM patients in the country, there is a lack of in-depth understanding of the situation.

Objective

To assess dietary practices and associated factors among adult DM patients at academic tertiary-level hospitals in central Ethiopia in 2024.

Methods

A concurrent mixed-methods study was conducted from January 01 to 30, 2024, involving 420 adult DM patients. Participants were selected using a simple random sampling technique for the quantitative study. A purposive sampling technique was used to select sixteen participants for qualitative analysis. For the quantitative study, a self-administered structured questionnaire was used to collect data, and in-depth interviews were conducted for the qualitative part. Multivariate binary logistic regressions were used to assess the explanatory variables associated with dietary practice. A thematic analysis was performed for qualitative data.

Result

Of 420 eligible participants, 406 (96.7%) participated in the study. The overall proportion of good dietary practices among participants was 172 (42.4%). Being female, residing in urban areas, having a family history of DM, and having good dietary knowledge were significantly associated with better dietary practices. From the qualitative analysis, two themes emerged "Living as before and not adhering to diabetic dietary recommendations" and "Barriers to adherence to effective eating practices."

Conclusions and recommendations

Less than half of adult DM patients had good dietary practices. Sex, geographic location, family history of DM, and level of knowledge of diabetic diet were associated with dietary practice. Intervention programs on awareness creation and training to improve the dietary practice by stakeholders were recommended.
Efficacy and safety of the needle rendezvous technique for infrainguinal arterial calcified lesions
Authors: Haraguchi Takuya , Tsujimoto Masanaga , Kashima Yoshifumi , Kasai Yuhei , Sato Katsuhiko , Fujita Tsutomu
Published: October 2024

Background

Lower extremity artery disease is increasingly prevalent, and complex lesions such as calcified chronic total occlusions pose significant challenges during endovascular therapy. The needle rendezvous technique, which involves puncturing a needle toward the guidewire within the lesion or lumen and advancing the guidewire into the needle lumen to achieve guidewire externalization, offers a potential solution. If device passage remains challenging, the Rendezvous-PIERCE technique can be subsequently employed by advancing the needle over the externalized guidewire to modify the lesion directly. This study aimed to evaluate the procedural outcomes of needle rendezvous in infrainguinal arterial occlusive lesions.

Methods

This single-center, retrospective, single-arm study included patients treated with needle rendezvous between August 2020 and March 2024. The primary outcome was technical success rate, defined as the device passage following guidewire externalization using needle rendezvous. Secondary outcomes included the rates of procedural success, complications, and 30-day clinical-driven target lesion revascularization (CDTLR).

Results

Twenty-five patients (25 limbs) with 52% on hemodialysis and 80% having chronic limb-threatening ischemia in 52% and 80% were enrolled. All cases involved bilateral calcified occlusions, and 72% targeted the infrapopliteal artery segment. The average needle rendezvous time was 3.7 ± 2.0 min. Rendezvous-PIERCE was performed in 28% of cases. All cases achieved 100% technical and procedural success, with no procedure-related complications. The 30-day CDTLR rate was 8%, limited to below-the-knee lesions.

Conclusions

Needle rendezvous is a safe and effective technique for treating complex infrainguinal arterial occlusions, providing a viable alternative when conventional methods fail.
Iatrogenic botulism after intragastric botulinum neurotoxin injections – a major outbreak
Authors: Goerttler Tsepo , Dorner Martin B. , van der Linden Christina , Kienitz Ricardo , Petrik Stephan , Blechinger Stephan , Spickschen Jonah , Betz Iris R. , Hinrichs Carl , Steindl David , Weber Frederike , Musacchio Thomas , Wunderlich Gilbert , Rueger Maria Adele , Barbe Michael T. , Dafsari Haidar , Demir Seda , Lapa Sriramya , Zeiner Pia S. , Strzelczyk Adam , Tinnemann Peter , Kleine Christian , Totzeck Andreas , Klebe Stephan , Mikolajewska Agata , Dorner Brigitte G. , Fertl Elisabeth , Grefkes-Hermann Christian , Fink Gereon , Kleinschnitz Christoph , Hagenacker Tim
Published: October 2024

Background

Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI.

Methods

We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany.

Results

Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits.

Conclusion

Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.
Side effects of insecticides used for management of
Tuta absoluta
Meyrick (Lepidoptera: Gelechidae) on the biocontrol agent
Trichogramma brassicae
Bezdenko (Hymenoptera: Trichogrammatidae)
Authors: Papari Salma , Dousti AbuFazel , Fallahzadeh Majid , Haddi Khalid , Desneux Nicolas , Saghaei Nazila
Published: October 2024

Trichogramma brassicae
is one of the most important egg parasitoids of many pests including South American tomato pinworm,
Tuta absoluta
(Lepidoptera: Gelechiidae). In agrosystems, the function of parasitoids can be affected by the application of insecticides. To use biological control agents and pesticides simultaneously in pest management, it is necessary to know the potential effect of pesticides on biological control agents. In this study, the lethal and sublethal effects of four insecticides (flubendiamide, emamectin benzoate + lufenuron, thiocyclam, and spinosad) frequently used to control
T. absoluta
, were investigated on its parasitoid
Trichogramma Brassicae
Bezdenko (Hymenoptera: Trichogrammatidae), under controlled laboratory conditions. The results showed that spinosad with an LC
50
value of 0.73 mg a.i./ L was highly toxic against adults of
T. brassicae
in comparison to flubendiamide (4.09 mg a.i./ L), emamectin benzoate + lufenuron (4.17 mg a.i./ L), and thiocyclam (9.59 mg a.i./ L). Furthermore, key demographic parameters such as net reproductive rate (
R
0
), intrinsic rate of increase (
r
m
), mean generation time (
T
), and doubling time (DT) were significantly decreased after exposure of
T. brassicae
to the LC
30
s of spinosad, thiocyclam, flubendiamide, and emamectin benzoate + lufenuron compared to the control. In the light of our results, the four insecticides should be used cautiously in
T. absoluta
integrated management programs. While the thiocyclam can be combined with the
T. brassicae,
the flubendiamide and emamectin benzoate + lufenuron are not recommended in the presence of this parasitoid. The use of spinosad should be avoided concomitantly with the release of
T. brassicae
.
Positron Emission Tomography Imaging of Pheochromocytoma and Paraganglioma—18F-FDOPA vs Somatostatin Analogues
Authors: Ebbehoj Andreas , Iversen Peter , Kramer Stine , Stochholm Kirstine , Poulsen Per Løgstrup , Hjorthaug Karin , Søndergaard Esben
Published: October 2024

Context

Functional imaging with positron emission tomography (PET) scans is an essential part of the diagnostic workup for pheochromocytoma and paraganglioma (PPGL). The purpose of this review is to (1) provide a brief overview of functional imaging for PPGL, (2) summarize selected present and older guideline and review recommendations, and (3) conduct a literature review on the diagnostic performance of the most used PET tracers for PPGL.

Evidence Acquisition

We conducted a systematic literature search in PubMed from January 2004 to August 2024 with the search string (“Pheochromocytoma” OR “Paraganglioma”) AND (“Positron Emission Tomography” OR “Radionuclide Imaging” OR (“PET” AND (“FDG” OR “DOTATOC” OR “DOTANOC” OR “DOTATATE” OR “DOPA” OR “FDOPA”))). Studies involving PET scans of at least 20 individuals with PPGL or at least 5 individuals in a rare, well-defined subgroup of PPGL (eg, sympathetic or head-neck paragangliomas and specific pathogenic variants) were included.

Evidence Synthesis

Seventy studies were identified of which 21 were head-to-head comparisons of at least 2 different PET tracers [18F-fluorodihydroxyphenylalanine, fluorodihydroxyphenylalanine positron emission tomography (18F-FDOPA), 68Ga-DOTA-conjugated somatostatin analogues, 68Ga-DOTA-conjugated somatostatin analogue positron emission tomography (68Ga-SSA), and 18F-fluorodeoxyglucose]. 18F-FDOPA had higher sensitivity for pheochromocytoma compared to 68Ga-SSA and equal sensitivity for metastatic pheochromocytoma. 18F-FDOPA and 68Ga-SSA had similar sensitivity for primary non-succinate dehydrogenase subunits (SDHx) sympathetic and head-neck paraganglioma. However, 68Ga-SSA had higher sensitivity for metastatic sympathetic and head-neck paraganglioma and for SDHx-related paraganglioma.

Conclusion

18F-FDOPA and 68Ga-SSA PET are both sensitive for localizing PPGL. However, 18F-FDOPA is the most sensitive for detecting pheochromocytoma, while 68Ga-SSA is superior to 18F-FDOPA for metastatic sympathetic and head-neck paraganglioma and SDHx-related paraganglioma.
Flight power muscles have a coordinated, causal role in controlling hawkmoth pitch turns
Authors: Wood Leo J. , Putney Joy , Sponberg Simon
Published: October 2024

Flying insects solve a daunting control problem of generating a patterned and precise motor program to stay airborne and generate agile maneuvers. In this motor program, each muscle encodes information about movement in precise spike timing down to the millisecond scale. Whereas individual muscles share information about movement, we do not know whether they have separable effects on an animal's motion, or whether muscles functionally interact such that the effects of any muscle's timing depend heavily on the state of the entire musculature. To answer these questions, we performed spike-resolution electromyography and electrical stimulation in the hawkmoth Manduca sexta during tethered flapping. We specifically explored how flight power muscles contribute to pitch control. Combining correlational study of visually induced turns with causal manipulation of spike timing, we discovered likely coordination patterns for pitch turns, and investigated whether these patterns can drive pitch control. We observed significant timing change of the main downstroke muscles, the dorsolongitudinal muscles (DLMs), associated with pitch turns. Causally inducing this timing change in the DLMs with electrical stimulation produced a consistent, mechanically relevant feature in pitch torque, establishing that power muscles in M. sexta have a control role in pitch. Because changes were evoked in only the DLMs, however, these pitch torque features left large unexplained variation. We found this unexplained variation indicates significant functional overlap in pitch control such that precise timing of one power muscle does not produce a precise turn, demonstrating the importance of coordination across the entire motor program for flight.
Sustainability performance assessment of sago industry supply chain using a multi-criteria adaptive fuzzy inference model
Authors: Yusmiati Yusmiati , Machfud Machfud , Marimin Marimin , Sunarti Titi Candra
Published: October 2024

Background Sustainable supply chains are more competitive than conventional supply chains. Supply chain sustainability performance needs to be carried out to determine sustainability under current conditions and to design appropriate strategies to increase sustainability. This study aims to design a sustainability performance assessment model for the sago agro-industry supply chain and identify critical indicators for sustainability improvement. Methods The Fuzzy Inference System (FIS) evaluates sustainability on three levels: economic, social, and environmental. The Adaptive Neuro-Fuzzy Inference System (ANFIS) is then used to aggregate the overall sustainability performance. The cosine amplitude method (CAM) was used to analyze key indicators. This study assessed the sustainability performance on industrial- and small-medium-scale sago agro-industry. Results The results show that the supply chain sustainability performance on the industrial scale is 44.25, while it is 48.81 for the small-medium scale with the same status, almost sustainable. Key indicators for improving sago agro-industry supply chain sustainability performance include profit distribution among supply chain actors, institutional support for supply chains, waste utilization (reuse & recycle), and the availability of waste management facilities. The implication of this research for managers regards assessing the current status of sustainability performance and key indicators as a reference for formulating sustainability strategies and practices. Implication The sago agro-industry sustainability performance evaluation methodology uses industry-relevant metrics to assess supply chain sustainability, promoting collaboration among stakeholders and assisting in the creation of sustainable strategies. Conclusions The results of the study will enable supply chain actors to understand the key indicators for improving sustainability performance in the sago agro-industry supply chain, especially in Meranti Islands Regency, Riau Province. The proposed model can be applied to other agro-industries by adjusting the indicators used and assessing data availability and suitability for the research object.
Recent Advances in Biopesticide Research and Development with a Focus on Microbials
Authors: Tadesse Mawcha Kahsay , Malinga Lawrence , Muir Debbie , Ge Jing , Ndolo Dennis
Published: October 2024

Biopesticides are pest control products derived from natural sources such as microbes, macro-organisms (insects and pathogens), plant extracts, and certain minerals. Many biopesticides are considered environmentally safe and can complement or substitute conventional chemical pesticides. They can also be highly specific or broad spectrum with a unique mode of action controlling a wide range of pest species. Due to their target-specificity and low to no environmental residuality, biopesticides conform to the 3 pillars of Climate-Smart Agriculture, the Sustainable Development Goals, and, ultimately, the Paris Agreement. This review focuses largely on microbial biopesticides derived from fungi, bacteria, viruses, and nematodes. It discusses (i) the various microbial biopesticide formulations, (ii) the mode of microbial biopesticide action, (iii) the factors that affect the potential efficacy of biopesticides, (iv) challenges to the adoption of microbial biopesticides, and (v) the role of microbial biopesticides in Integrated Pest Management programs. Finally, advancements in application techniques, as well as future research directions and gaps, are highlighted.