bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Ethnomedical Use Data to the Marketing Authorization of Traditional Herbal Medicines in Mali
Authors: Sangho Aboubacar , Ouoba Kampadilemba , Semdé Rasmané , Sanogo Rokia
Published: October 2024

Background

To improve the supply of health care and health care products, traditional herbal medicines that are safe, effective, and of good quality need marketing authorizations. This study aims to determine the contribution of ethnomedical evidence to the marketing of traditional herbal medicines in Mali.

Methods

This was a descriptive cross-sectional study conducted from December 2023 to March 2024 supplemented by a literature review of the legislative and regulatory provisions relating to traditional medicine and the requirements for marketing authorization of traditional herbal medicines in Mali and the West African sub-region.

Results

The regulatory framework for marketing authorization is governed by decree no. 04-557/P-RM of 01 December 2004 and interministerial order no. 05-2203/MS-MEP-SG of 20 September 2005 in Mali. These texts set out the specific requirements for the marketing authorization of traditional plant-based medicines, depending on the category. They consider ethnomedical evidence drawn from long experience of traditional use as proof of efficacy and tolerance for category 2 traditional medicines. As a result, marketing authorizations were issued for 15 products derived from traditional medicine and pharmacopeia, 5 of which are included in the National List of Essential Medicines and the National Therapeutic Formulary of Mali.

Conclusion

The use of ethnomedical evidence provides a good opportunity to obtain marketing authorization for phytomedicines derived from traditional medicine without having to go through long and costly non-clinical and clinical studies.
Recombinant Erwinia asparaginase (JZP458) in ALL/LBL: complete follow-up of the Children’s Oncology Group AALL1931 study
Authors: Maese Luke , Loh Mignon L. , Choi Mi Rim , Agarwal Shirali , Aoki Etsuko , Liang Yali , Lin Tong , Girgis Suzette , Chen Cuiping , Roller Shane , Chandrasekaran Vijayalakshmi , Iannone Robert , Silverman Lewis B. , Raetz Elizabeth A. , Rau Rachel E.
Published: October 2024

Children’s Oncology Group study AALL1931 investigated the efﬁcacy and safety of recombinant Erwinia asparaginase (JZP458) in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma and hypersensitivity reactions/silent inactivation to Escherichia coli–derived asparaginases. Each pegylated Escherichia coli asparaginase dose remaining in a patient’s treatment plan was replaced by intramuscular (IM) or IV JZP458 (6 doses) administered Monday/Wednesday/Friday (MWF). Three IM cohorts (1a [25 mg/m2 MWF], n = 33; 1b [37.5 mg/m2 MWF], n = 83; 1c [25/25/50 mg/m2 MWF], n = 51) and 1 IV cohort (25/25/50 mg/m2 MWF, n = 62) were evaluated. The proportion (95% confidence interval [CI]) of patients maintaining nadir serum asparaginase activity (NSAA) levels of ≥0.1 IU/mL at the last 72 (primary end point) and 48 hours during course 1 was 90% (95% CI, 81-98) and 96% (95% CI, 90-100) in IM cohort 1c, respectively, and 40% (95% CI, 26-54) and 90% (95% CI, 82-98) in the IV cohort. Population pharmacokinetic modeling results were comparable with observed data, predicting the vast majority of patients would maintain therapeutic NSAA levels when JZP458 is administered IM or IV 25 mg/m2 every 48 hours, or IM 25/25/50 mg/m2 MWF, or with mixed IM and IV administration (IV/IV/IM 25/25/50 mg/m2 MWF). Drug discontinuation occurred in 23% and 56% of patients in the IM and IV cohorts, respectively; 13% and 33% because of treatment-related adverse events (mainly allergic reactions and pancreatitis). JZP458 achieves therapeutic NSAA levels via multiple IM and IV dosing schedules based on combined observed and modeled data with a safety profile consistent with other asparaginases. This trial was registered at www.ClinicalTrials.gov as #NCT04145531.
Assessment of nursing managers’ awareness and hospital preparedness for disasters: a cross-sectional study
Authors: Rahimi Borhan , Yari Arezoo , Rafiei Fatemeh , Mahmoudi Mokhtar
Published: October 2024

Introduction

Preparedness, focused on planning, training, and research, is one of the primary stages of the disaster management cycle. Accordingly, this study was conducted to determine the level of awareness in nursing managers and the preparedness of hospitals for disasters in the hospitals of Sanandaj, the capital of Kurdistan Province.

Methods

This cross-sectional study was conducted in 2023, with a total of 167 Nursing Managers in Sanandaj selected as the research sample using a census approach. Data were collected using a demographic information form, WHO Hospital Emergency Response Checklist, and managers’ emergency awareness questionnaire. Data were analyzed using Chi-square tests, Fisher’s exact test, independent t-tests, analysis of variance (ANOVA), and Pearson correlation. Data analysis was performed using SPSS v26 (P < 0.05).

Findings

The results indicated that the overall mean score of managers’ awareness was 77.89%, categorized as good. The assessment of hospital preparedness showed that the overall emergency preparedness level of hospitals in Sanandaj was 69.23%, considered strong. Among the dimensions of hospital preparedness, the highest score was in the command-and-control dimension at 83.33%, while the lowest was in the human resources dimension at 56.66%.

Conclusion

The findings indicated a high level of awareness among nursing managers and a strong level of hospital preparedness in Sanandaj. However, improving and enhancing specific dimensions may require targeted educational and organizational approaches.
Longitudinal mediation analysis with multilevel and latent growth models: a separable effects causal approach
Authors: Di Maria Chiara , Didelez Vanessa
Published: October 2024

Background

Causal mediation analysis is widespread in applied medical research, especially in longitudinal settings. However, estimating natural mediational effects in such contexts is often difficult because of the presence of post-treatment confounding. Moreover, many models frequently used in applied research, like multilevel and latent growth models, present an additional difficulty, i.e. the presence of latent variables. In this paper, we propose a causal interpretation of these two classes of models based on a novel type of causal effects called separable, which overcome some of the issues of natural effects.

Methods

We formally derive conditions for the identifiability of separable mediational effects and their analytical expressions based on the g-formula. We carry out a simulation study to investigate how moderate and severe model misspecification, as well as violation of the identfiability assumptions, affect estimates. We also present an application to real data.

Results

The results show how model misspecification impacts the estimates of mediational effects, particularly in the case of severe misspecification, and that the bias worsens over time. The violation of assumptions affects separable effect estimates in a very different way for the mixed effect and the latent growth models.

Conclusion

Our approach allows us to give multilevel and latent growth models an appealing causal interpretation based on separable effects. The simulation study shows that model misspecification can heavily impact effect estimates, highlighting the importance of careful model choice.
Changes in BMI prior to and during the COVID-19 pandemic among children: a retrospective cohort study in San Francisco, CA
Authors: Maxwell Sarah L. , McCulloch Charles E. , Fernandez Alicia , Beck Amy L.
Published: October 2024

Background

The COVID-19 pandemic led to dramatic changes in the lives of children that impact cardiometabolic health. Cities and counties had varying policies with respect to school closure, recreational programs, and efforts to mitigate food insecurity and economic distress. Our objective was to evaluate changes in BMI-z score and prevalence of overweight/obesity prior to and during the pandemic among children in San Francisco, CA, where public schools were closed for 18-months.

Methods

This was an electronic medical record-based retrospective cohort study. We included 15,401 children, 4–17 years of age at study onset. Our exposure was time into each of three time periods: (1) March 2018-February 2019; (2) March 2019-February 2020; (3) March 2020-August 2021 (the pandemic period of school closure). Generalized estimating equations (GEE) were used to assess changes in BMI-z score and overweight/obesity across the three time periods. We assessed for effect modification by age-category, insurance status, and race/ethnicity.

Results

Mean BMI-z score increased by 0.06 per year in time period 2, the year prior to the pandemic (p < 0.001, 95% CI: 0.04, 0.09), and by 0.12 per year during time period 3, the first 18 months of the pandemic (p < 0.001, 95% CI 0.10, 0.13). The proportion of children with overweight/obesity increased by 1.4% points per year during time period 2 (p = 0.012, 95% CI: 0.03, 2.46) and by 4.9% points per year during the first 18 months of the pandemic (p < 0.001, 95% CI: 4.11, 5.67). The effect modification analysis demonstrated that the youngest age group, publicly insured children (versus privately insured), and Black, Latino, and Asian children (versus White children) experienced greater increases in BMI-z score during the pandemic (p < 0.01 for all comparisons). The youngest age group (p = 0.022) and publicly insured children (versus privately insured children) (p < 0.001) also experienced greater increases in the proportion of children with overweight/obesity during the pandemic.

Conclusions

Among children in San Francisco, increases in BMI-z score and overweight/obesity were greater during the pandemic compared to prior changes, with the most pronounced increases among younger and publicly insured children. These findings support the need for more targeted and effective policies for addressing childhood overweight/obesity, especially among these high-risk populations.
Intravenous injection versus transhepatic intracholecystic injection of indocyanine green (ICG) to outline biliary tree during laparoscopic cholecystectomy
Authors: Elmeligy Hesham A. , Hassan Hend F. , Amer Moshira S. , Ossama Yousra , Maher Mohamed A. , Azzam Ahmed M. , Rady Mahmoud
Published: October 2024

Background

To potentially lessen injuries and associated complications, fluorescence cholangiography has been suggested as a technique for enhancing the visualization and identification of extrahepatic biliary anatomy. The most popular way to administer indocyanine green (ICG) is intravenously, as there is currently little data on ICG injections directly into the gallbladder. In order to visualize extrahepatic biliary anatomy during laparoscopic cholecystectomy (LC), we compared the two different ICG administration techniques. We also examined variations in visualization time, as well as the effectiveness, benefits, and drawbacks of each modality.

Methods

In this prospective randomized clinical study, 60 consecutive adult patients with chronic and acute gallbladder disease were included. Our study conducted from 2022 to 2024 in Surgical Department of Theodor Bilharz Research Institute. Thirty patients underwent LC with intravenous ICG administration (IV-ICG), thirty patients received a direct injection of gallbladder through transhepatic ICG (IC-ICG) and Preoperative, intraoperative, and postoperative patient data were examined.

Results

In terms of their perioperative and demographic features, the groups were similar. Without a statistically significant difference, the IV-ICG group’s total operating time was less than that of the IC-ICG group (p 0.140). Compared to the transhepatic IC-ICG method, IV-ICG was more accurate in identifying the duodenum and the common hepatic duct (p = 0.029 and p = 0.016, respectively). In the transhepatic IC-ICG and IV-ICG groups, the cystic duct could be identified prior to dissection in 66.6% and 73.3% of cases, respectively, and this increased to 86.6% and 93.3% following dissection. In the transhepatic IC-ICG group, the common bile duct was visible in 93.3% of cases; in the IV-ICG group, it was visible in 90% of cases. Two cases in the IC-ICG group and every case following IV-ICG administration had liver fluorescence (6.6% versus 100%; p < 0.001).

Conclusion

The current study shows that for both administration methods, ICG-fluorescence cholangiography can be useful in identifying the extrahepatic biliary anatomy during Calot’s triangle dissection. By avoiding hepatic fluorescence, the transhepatic IC-ICG route can increase the bile duct-to-liver contrast with less expense and no risk of hypersensitivity reactions than the intravenous ICG injection method. We recommend to use both techniques in case of acute cholecystitis with cystic duct obstruction. In cases of liver cirrhosis, we recommend transhepatic IC-ICG as IV-ICG is limited.
Fiber post cemented using different adhesive strategies to root canal dentin obturated with calcium silicate-based sealer
Authors: Patthanawijit Lalita , Yanpiset Kallaya , Saikaew Pipop , Jantarat Jeeraphat
Published: October 2024

Background

Calcium silicate-based sealer has favorable properties for root canal filling, including hydroxyapatite formation during the setting process. However, this process can cause difficulty during post space preparation when the sealer is set. Additionally, the remaining sealer could interfere with the bond strength of fiber post to root canal dentin. The different adhesive strategies and fiber post cementation time may affect the bond strength of the fiber post. Thus, the objective of this study was to evaluate the effect of etching modes of Scotchbond™ Universal Plus adhesive and post cementation time on the push-out bond strength of a fiber post cemented in root canals obturated with calcium silicate-based sealer.

Methods

Fifty-four teeth were randomly allocated to 6 groups (n = 9) based on etching modes: self-etch (SE) or etch-and-rinse (ER); post space preparation and cementation time: immediate (Im) or 7-day delayed (De): Im-Im, Im-De, and De-De. The root canals were obturated with calcium silicate-based sealer and the post space preparation was performed. The fiber post was cemented using RelyX™ Universal resin cement according to each group’s design. For the push-out bond strength test, 1-mm slices of the coronal, middle, and apical regions were tested using a universal testing machine. The failure mode analysis was determined using a stereomicroscope. The data was analyzed with three-way analysis of variance.

Results

No negative effects of etching modes, post space preparation or cementation time on push-out bond strength were detected (p > 0.05). Additionally, the root canal region also did not significantly affect the bond strength (p > 0.05).

Conclusion

No significant differences were observed between the etching modes, post space preparation and cementation time and among root canal regions.

Clinical relevance

The different etching modes of adhesive and post cementation time did not affect the bond strength of fiber post in calcium silicate filled-root canal.
Exploring molecular spectrum in thai patients with maple syrup urine disease: unveiling a common variant
Authors: Lakkhana Panisara , Tim-Aroon Thipwimol , Khongkraparn Arthaporn , Noojarern Saisuda , Wongkittichote Parith , Wichajarn Khunton , Kuptanon Chulaluck , Boonyawat Boonchai , Suphapeetiporn Kanya , Wejaphikul Karn , Seo GoHun , Wattanasirichaigoon Duangrurdee
Published: October 2024

Background

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand.

Results

A cross-sectional, multicenter study was conducted, including twenty Thai MSUD patients from 1997 to 2023. Most of the patients presented with classic neonatal onset (95%). The mortality rate was 20%, while global developmental delay was observed in 40% of the patients. Variants in the BCKDHB gene were detected in 85% (17/20) of the patients, while the BCKDHA gene accounted for 15% (3/20). The study identified the 11-kb deletion involving 5’UTR, exon 1, and intron 1 in the BCKDHB gene, from a position of g.80102385 to g.80113453 (NC_000006.12), accounting for 50% of all variants (20/40 alleles) in Thai MSUD patients. All patients with the 11-kb deletion in BCKDHB presented with the classic type. The gap-PCR for this common deletion was established in the study.

Conclusion

This study is the first to describe the clinical and molecular spectrum of Thai MSUD patients before the implementation of expanded NBS. The 11-kb deletion involving exon 1 in the BCKDHB emerges as the most common variant among Thai individuals with MSUD. Furthermore, the gap-PCR test for detecting the 11-kb exon 1 deletion status holds the potential for integration into stepwise molecular analysis following positive expanded newborn screening.
High PD-1 and CTLA-4 expression correlates with host immune suppression in patients and a mouse model infected with Echinococcus multilocularis
Authors: Sun Ting , Yang Yi , Qiu Yiwen , Wang Tao , Yang Ming , Shen Shu , Wang Wentao
Published: October 2024

Background

Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear.

Methods

We collected liver specimens from hepatic alveolar echinococcosis (HAE) patients and established a mouse model of E. multilocularis infection. Immunofluorescence staining and flow cytometry were performed to analyze programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) expression in human samples, while flow cytometry and quantitative real-time polymerase chain reaction (PCR) were performed for similar analyses in mouse samples. Cell proliferation and protoscolex (PSC) killing assays were designed to explore how E. multilocularis induces host immunosuppression.

Results

An inflammatory reaction band with high PD-1 and CTLA-4 expression was found in close liver tissue (CLT). The ratio of regulatory T cells (Tregs) was higher in CLT than in distant liver tissue (DLT), and Tregs in CLT tended to express higher levels of PD-1 and CTLA-4 than those in DLT from HAE patients. Echinococcus multilocularis-infected mice showed significantly elevated expression of PD-1 and CTLA-4 on splenocytes and peritoneal cells. PD-1/PD-L1 or CTLA-4 pathway blockade could relieve the immunosuppressive effects of Tregs from infected mice and enhance PSC killing by mouse splenocytes.

Conclusions

E. multilocularis regulated the function of T cells via the PD-1/PD-L1- and CTLA-4-dependent pathways and subsequently evaded host immune attacks. These findings provide insights for investigating the pathogenic mechanism of AE.

Graphical Abstract
Phosphodiesterase inhibition and Gucy2C activation enhance tyrosine hydroxylase Ser40 phosphorylation and improve 6-hydroxydopamine-induced motor deficits
Authors: Douma Erik H. , Stoop Jesse , Lingl Matthijs V. R. , Smidt Marten P. , van der Heide Lars P.
Published: October 2024

Background

Parkinson’s disease is characterized by a progressive loss of dopaminergic neurons in the nigrostriatal pathway, leading to dopamine deficiency and motor impairments. Current treatments, such as L-DOPA, provide symptomatic relief but result in off-target effects and diminished efficacy over time. This study explores an alternative approach by investigating the activation of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Specifically, we explore the effects of phosphodiesterase (PDE) inhibition and guanylate cyclase-C (GUCY2C) activation on tyrosine hydroxylase Ser40 phosphorylation and their impact on motor behavior in a 6-hydroxydopamine (6-OHDA) Parkinson's disease model.

Results

Our findings demonstrate that increasing cyclic nucleotide levels through PDE inhibition and GUCY2C activation significantly enhances tyrosine hydroxylase Ser40 phosphorylation. In a Pitx3-deficient mouse model, which mimics the loss of dopaminergic neurons seen in Parkinson’s disease, Ser40 phosphorylation remained manipulable despite reduced tyrosine hydroxylase protein levels. Moreover, we observed no evidence of tyrosine hydroxylase degradation due to Ser40 phosphorylation, challenging previous reports. Furthermore, both PDE inhibition and GUCY2C activation resulted in improved motor behavior in the 6-OHDA Parkinson’s disease mouse model, highlighting the potential therapeutic benefits of these approaches.

Conclusions

This study underscores the therapeutic potential of enhancing tyrosine hydroxylase Ser40 phosphorylation to improve motor function in Parkinson’s disease. Both PDE inhibition and GUCY2C activation represent promising non-invasive strategies to modulate endogenous dopamine biosynthesis and address motor deficits. These findings suggest that targeting cyclic nucleotide pathways could lead to novel therapeutic approaches, either as standalone treatments or in combination with existing therapies like L-DOPA, aiming to provide more durable symptom relief and potentially mitigate neurodegeneration in Parkinson's disease.
Numerical solution of nonlinear partial differential equations using shifted Legendre collocation method
Authors: Abbassi Passant K. , Fathy Mohamed , Elbarkoki R. A. , Abdelgaber K. M.
Published: October 2024

In life important applications are modeled mathematically by nonlinear partial differential equations. Primarily, the objective is to transform such equations into a system of algebraic equations to get their solutions. The Legendre collocation method is demonstrated by the differentiation operational matrix via shifted Legendre polynomials in such a transformation. The validity and effectiveness of the prospective method are manifested by illustrative examples, an error analysis, residual analysis, and comparison with others.
Postoperative opioid use in Norway—a population-based observational study on patterns of long-term use
Authors: Vambheim Sara Magelssen , Hjellvik Vidar , Odsbu Ingvild , Skurtveit Svetlana , Ekholdt Christopher , Granan Lars Petter , Stubhaug Audun , Samuelsen Per-Jostein
Published: October 2024

Background

The utilization patterns of opioid analgesics and the proportion of long-term opioid use after surgery in Norway is largely unknown.

Methods

This study aimed to estimate the proportion of one-year long-term prescription opioid use among all Norwegian postoperative opioid users. Complete data from central health registries (NPR, NorPD, Statistics Norway, CoDR) were linked via the personal identification number unique to all citizens. The study period was January 1st 2010 until December 31st 2019. Long-term opioid use was defined as at least two opioid dispensings within two subsequent 90-day periods, with a minimum average use of 10 MME/day for the first 90 days.

Results

The study population consisted of 693 495 post-operative opioid users (53.6% women), whereof 73.2% had not used opioids the year before surgery (new users). Among the postoperative opioid users, 3.8% were one-year long-term opioid users. The corresponding figures for new and previous opioid users were 0.4% and 13.1%, respectively. The highest proportions of long-term opioid use were found after transluminal endoscopy, eye surgery and assessments related to surgical procedures. In previous opioid users, the proportion of one-year long-term use was higher among women than men in all age groups, a difference that increased with age.

Conclusions

The proportion of postoperative long-term opioid use in Norway is generally low. We detected higher proportions of long-term opioid use after certain types of surgery, but our crude surgery definition warrants further examination. Previous opioid users pose a particular challenge in the management of postoperative pain.

Trial registration

The study used national health registry data from the period 2010–2019. A pre-registered analysis plan is available at Open Science Framework.
Association between leisure-time physical activity and incident cancer risk: a nationwide population-based cohort study
Authors: Lai Yun-Ju , Wang Chun-Chieh , Lin Yu-Kai , Chen Mei-Ju , Chou Yi-Sheng , Chen Chu-Chieh , Liu Chieh-Yu , Wu Shang-Jung , Hsu Li-Fei , Li Jia-Hua , Yen Yung-Feng
Published: October 2024

Background

The effects of physical activity on the development of different types of cancers have not been comprehensively studied. This nationwide, population-based cohort study investigated the effects of leisure-time physical activity (LTPA) on the development of different types of cancer in Taiwanese adults. A total of 67,890 adult participants (≥ 18 y old) from five rounds (2001, 2005, 2009, 2013, and 2017) of the Taiwan National Health Interview Survey were included. LTPA was measured as the metabolic equivalent of task (MET) expenditure per week and was classified as inactive (< 1 MET-h), low (1-7.49 MET-h), or high (≥ 7.5 MET-h). The LTPA and other covariates were collected through in-person interviews at baseline. New-onset cancer was ascertained from histopathological reports. The Fine-Gray sub-distribution method, with death as a competing risk, was used to determine the impact of LTPA on incident cancer risk.

Results

During the 844,337 person-years of follow-up, 4,435 individuals developed cancer. Compared to inactive adults, individuals engaging in high levels of LTPA (≥ 7.5 MET-h/week) were significantly associated with a reduced risk of developing cancer (adjusted hazard ratio [aHR] = 0.93; 95% confidence interval [CI] = 0.87–0.99). However, those with low levels of LTPA (1-7.49 MET-h/week) did not exhibit a significant association with a reduced risk of developing cancer (aHR = 1.00; 95% CI = 0.92–1.10). When considering specific types of cancers, participants with high levels of LTPA (≥ 7.5 MET-h/week) had a significantly lower risk of developing bladder cancer (aHR = 0.68; 95% CI = 0.47–0.99), cervical cancer (aHR = 0.48; 95% CI = 0.24–0.95), and thyroid cancer (aHR = 0.64; 95% CI = 0.44–0.93).

Conclusions

Our findings suggest that high LTPA (≥ 7.5 MET-h/week) is significantly associated with a low risk of incident bladder, cervical, and thyroid cancers.
Programming rumen microbiome development in calves with the anti-methanogenic compound 3-NOP
Authors: Martinez-Fernandez Gonzalo , Denman Stuart E. , Walker Nicola , Kindermann Maik , McSweeney Christopher S.
Published: October 2024

The aim of this study was to establish a distinctive rumen microbial and fermentation profile using the anti-methanogenic compound 3-NOP to assess dam effect, and nutritional intervention of the juvenile offspring on microbial structure and function of rumen up to 12 months of age, once the treatment was withdrawn. Forty-eight pregnant heifers (H) and their future offspring (C) were allocated to either Control (-) or 3-NOP (+) treatment resulting in four experimental groups: H+/C+, H+/C-, H-/C + and H-/C-. Animals were treated from 6 weeks prior to calving until weaning, with the offspring monitored until 12 months of age. Rumen fluid samples and methane measurements using the Greenfeed system were collected during the trial. Results supported the mode of action of the compound, with a shift in fermentation from acetate to propionate, increases in branched chain fatty acids and formic acid in the 3-NOP treated animals. Similar shifts in microbial populations occurred in 3-NOP treated animals with lower abundances of rumen methanogen populations, increases of bacterial groups Succiniclasticum spp, Candidatus Saccharimonas. Fibrobacter and the families Prevotellaceae and Succinivibrioacea. and the protozoa Entodinium. Early life intervention had an enduring impact on the rumen microbial structure of young animals up to 28 weeks post weaning, however the effect was diminished once 3-NOP was withdrawn. Interestingly, a group of young animals emitted significantly less methane (15%) than the animals that did not receive the treatment during their juvenile stage. Our results suggest a higher resemblance of the young calf microbiome to a low methane adult and that early life colonisation of the rumen persists through to later life with the pre-weaning microbiome comprising ~ 65% of the yearling animal. Further research needs to be performed to determine the timing and dose of 3-NOP for new-born calves that can sustain a reduction in methane emissions after the treatment is withdrawn, under extensive grazing or controlled conditions.
Ruminant microbiome data are skewed and unFAIR, undermining their usefulness for sustainable production improvement
Authors: Ortiz-Chura Abimael , Popova Milka , Morgavi Diego P.
Published: October 2024

The ruminant microbiome plays a key role in the health, feed utilization and environmental impact of ruminant production systems. Microbiome research provides insights to reduce the environmental footprint and improve meat and milk production from ruminants. However, the microbiome composition depends on the ruminant species, habitat and diet, highlighting the importance of having a good representation of ruminant microbiomes in their local environment to translate research findings into beneficial approaches. This information is currently lacking. In this study, we examined the metadata of farmed ruminant microbiome studies to determine global representativeness and summarized information by ruminant species, geographic location, body site, and host information. We accessed data from the International Nucleotide Sequence Database Collaboration via the National Center for Biotechnology Information database. We retrieved 47,628 sample metadata, with cattle accounting for more than two-thirds of the samples. In contrast, goats, which have a similar global population to cattle, were underrepresented with less than 4% of the total samples. Most samples originated in Western Europe, North America, Australasia and China but countries with large ruminant populations in South America, Africa, Asia, and Eastern Europe were underrepresented. Microbiomes from the gastrointestinal tract were the most frequently studied, comprising about 87% of all samples. Additionally, the number of samples from other body sites such as the respiratory tract, milk, skin, reproductive tract, and fetal tissue, has markedly increased over the past decade. More than 40% of the samples lacked basic information and many were retrieved from generic taxonomic classifications where the ruminant species was manually recovered. The lack of basic information such as age, breed or sex can limit the reusability of the data for further analysis and follow-up studies. This requires correct taxonomic assignment of the ruminant host and basic metadata information using accepted ontologies adapted to host-associated microbiomes. Repositories should require this information as a condition of acceptance. The results of this survey highlight the need to encourage studies of the ruminant microbiome from underrepresented ruminant species and countries worldwide. This shortfall in information poses a challenge for the development of microbiome-based strategies to meet sustainability requirements, particularly in areas with expanding livestock production systems.
Design, synthesis, and anticancer evaluation of novel N-[5-(1,3,4,5-tetrahydroxycyclohexyl)-1,3,4-thiadiazole-2-yl] benzamide analogues through integrated computational and experimental approaches
Authors: Jayaraj Sujaritha , Hemalatha K.
Published: October 2024

Background

The main aim of the current study is to develop, synthesize, in silico, in vitro and in vivo potentials of N-[5-(1,3,4,5-tetrahydroxycyclohexyl)-1,3,4-thiadiazole-2-yl] benzamide derivatives for a possible anticancer drug to improve their efficiency and selectivity against cancer cells, computational approaches aided in the rational design of these chemicals. Spectroscopic methods verified the chemical structures of the target compounds. The structures of the synthesized analogs were determined by elemental analysis, IR, 1H NMR, 13C NMR and MS. Structure shows the presence of 1,3,4, thiadiazole also responsible for anticancer activity. The 10 analogs were synthesized and showed encouraging anticancer efficacy in preliminary biological evaluation, suggesting they might be suitable lead candidates for more optimization and preclinical exploration.

Result

N-[5-(1,3,4,5-tetrahydroxycyclohexyl)-1,3,4-thiadiazole-2-yl] benzamide derivatives were synthesized (5a-5j) showed an optimum IC50 value in in vitro activity by SRB assay using MCF-7 as a strain, and the few selected analogs 5b,5 g & 5 h were subjected for in vivo anticancer activity by DMBA induction of tumors in mice.

Conclusion

Through a computational and experimental approach, this study results a way for newer derivatives for the class of anticancer drugs.
“Broadening Perspectives Activities” Improve LGBTQ+ Student Experiences and Religious Students’ Content Comprehension
Authors: Jackson Danny , Yule Kelsey , Biera Alex , Hawley Caitlin , Lacson Jason , Webb Emily , McGraw Kevin , Cooper Katelyn M.
Published: October 2024

We developed Broadening Perspective Activities (BPAs) to expand the representation of LGBTQ+ perspectives in an undergraduate Animal Behavior course. We found that the BPAs improved LGBTQ+ students' sense of belonging in biology, and improved comprehension of many concepts related to sex, gender, and sexuality across identities.
Redefining Available Therapy in Oncology Accelerated Approval Decisions
Authors: Patel Shruti Rajesh , Ramachandran Maya , Ai Angela , Chen Christopher T.
Published: October 2024

When weighing rapid approval for follow-on drugs, should @FDAOncology recognize the drugs that came before?
An Unusual Movement Disorder—Case of Diabetic Striatopathy
Authors: Azmat Shazia , Lodhi Owais , Ashok Harish , Harb Hussein , Siddiqui Mahwash , Gilden Janice
Published: October 2024

Nonketotic hyperglycemia chorea-ballismus (NKH-CB), a rare metabolic syndrome, arises as a secondary condition to hyperglycemia. It is marked by acute or subacute hemichorea-hemiballismus, hyperglycemic state, and unique reversible striatal abnormalities on neuroimaging. This case presents a 70-year-old Hispanic man with a significant medical history of cerebral vascular accidents, hypertension, bipolar disease, and uncontrolled type 2 diabetes mellitus.

Notably, the patient was experiencing large-amplitude involuntary movements on his left side for the past 3 weeks. With resolution of hyperglycemia, the amplitude and frequency of the involuntary arm movements were absent. This case highlights the need for careful monitoring and tight control of blood glucose levels in patients with a history of diabetes, to prevent serious neurological complications such as NKH-CB syndrome. Prompt diagnosis through neurological evaluation, blood glucose level assessment, and neuroimaging techniques are critical in managing the symptoms effectively.
Tributyltin Enhances Macrophage Inflammation and Lipolysis, Contributing to Adipose Tissue Dysfunction
Authors: Chang Richard C , Whitlock Ryan Scott , Joloya Erika , To Kaitlin Thanh , Huang Yikai , Blumberg Bruce
Published: October 2024

Tributyltin (TBT) is a synthetic chemical widely used in industrial and commercial applications. TBT exposure has been proven to elicit obesogenic effects. Gestational exposure led to increased white adipose tissue depot size in exposed (F1, F2) animals and in unexposed generations (F3, F4), an example of transgenerational inheritance. TBT exerts these effects in part by increasing the number and size of white adipocytes, altering the fate of multipotent mesenchymal stromal stem cells to favor the adipocyte lineage, altering adipokine secretion, and modulating chromatin structure. Adipose tissue resident macrophages are critical regulators in adipose tissue; however, the effects of TBT on adipose tissue macrophages remained unclear. Here we investigated the effects of TBT on macrophages and consequent impacts on adipocyte function. TBT significantly enhanced palmitate-induced inflammatory gene expression in mouse bone marrow derived macrophages and this effect was attenuated by the antagonizing action of the nuclear receptor peroxisome proliferator activated receptor gamma. TBT-treated macrophages decreased lipid accumulation in white adipocytes differentiated from mesenchymal stromal stem cells accompanied by increased expression of lipolysis genes. Lastly, ancestral TBT exposure increased Tnf expression in adipose tissue resident macrophages in both exposed (F2) and unexposed (F3) generations, suggesting that TBT exposure led to an inherited predisposition toward inflammatory adipose tissue macrophages that can manipulate adipose tissue function. These findings provide new insights into the interplay between adipocytes and adipose tissue macrophages in obesity, further establishing a role for obesogens such as TBT in the development of obesity-related metabolic disorders.
Defining Postinduction Hemodynamic Instability With an Automated Classification Model
Authors: Kho Eline , Immink Rogier V. , van der Ster Bjorn J.P. , van der Ven Ward H. , Schenk Jimmy , Hollmann Markus W. , Tol Johan T.M. , Terwindt Lotte E. , Vlaar Alexander P.J. , Veelo Denise P.
Published: October 2024

BACKGROUND:

Postinduction hypotension (PIH) may be associated with increased morbidity and mortality. In earlier studies, the definition of PIH is solely based on different absolute or relative thresholds. However, the time-course (eg, how fast blood pressure drops during induction) is rarely incorporated, whereas it might represent the hemodynamic instability of a patient. We propose a comprehensive model to distinguish hemodynamically unstable from stable patients by combining blood pressure thresholds with the magnitude and speed of decline.

METHODS:

This prospective study included 375 adult elective noncardiac surgery patients. Noninvasive blood pressure was continuously measured between 5 minutes before up to 15 minutes after the first induction agent had been administered. An expert panel rated whether the patient experienced clinically relevant hemodynamic instability or not. Interrater correlation coefficient and intraclass correlation were computed to check for consistency between experts. Next, an automated classification model for clinically relevant hemodynamic instability was developed using mean, maximum, minimum systolic, mean, diastolic arterial blood pressure (SAP, MAP, and DAP, respectively) and their corresponding time course of decline. The model was trained and tested based on the hemodynamic instability labels provided by the experts.

RESULTS:

In total 78 patients were classified as having experienced hemodynamic instability and 279 as not. The hemodynamically unstable patients were significantly older (7 years, 95% confidence interval (CI), 4–11, P < .001), with a higher prevalence of chronic obstructive pulmonary disease (COPD) (3% higher, 95% CI, 1–8, P = .036). Before induction, hemodynamically unstable patients had a higher SAP (median (first–third quartile): 161 (145–175) mm Hg vs 150 (134–166) mm Hg, P < .001) compared to hemodynamic stable patients. Interrater agreement between experts was 0.92 (95% CI, 0.89–0.94). The random forest classifier model showed excellent performance with an area under the receiver operating curve (AUROC) of 0.96, a sensitivity of 0.84, and specificity of 0.94.

CONCLUSIONS:

Based on the high sensitivity and specificity, the developed model is able to differentiate between clinically relevant hemodynamic instability and hemodynamic stable patients. This classification model will pave the way for future research concerning hemodynamic instability and its prevention.
Escaping from Casa Arana: The Murui-Muina Nation after the Amazon Rubber Boom
Authors: Aponte Oscar
Published: October 2024

The Amazon rubber boom (1850–1930) devastated Indigenous nations that had remained for centuries at the borders of European empires and the nation-states that replaced them in South America. The arrival of the Peruvian rubber company Casa Arana to the Igaraparaná and Caraparaná Rivers in 1899 marked the conquest and colonization of the Murui-Muina nation and their ancestral lands. This essay examines the escape of Murui-Muina clans from Casa Arana and the ethnogenesis of a new kind of Murui-Muina society in the municipality of Leguízamo, in Colombian Amazonia, where they resettled. It argues that although the fleeing clans managed to escape from Casa Arana, the continued contact with rubber tappers, Capuchin missionaries, and Colombian government officials during their flight introduced fundamental changes to Murui-Muina life. However, once settled in Leguízamo, they were able to recreate Murui-Muina life and became the basis of the Indigenous communities that exist today in the municipality. The first two sections follow the fleeing clans along the Putumayo and Caquetá Rivers during the first three decades of the twentieth century; the following section considers their arrival to Leguízamo; and the final section analyzes the ethnogenesis of a new kind of Murui-Muina society in the municipality during the second half of the twentieth century.
From Sugar Bush to Treaty Councils: Ozhaawashkodewekwe’s Career in the Upper Great Lakes
Authors: Macgillivray Emily J.
Published: October 2024

Anishinaabe women in the nineteenth-century upper Great Lakes inherited responsibilities through their doodem (clan), which included incorporating newcomers into their networks and caring for lands and waterways. Employing biography, this article focuses on Ozhaawashkodewekwe, a prominent Anishinaabe who attempted to transform the gender-specific resources of seasonal rounds into titled property at sugar camps and treaty councils. The various stages of Ozhaawashkodewekwe’s life illustrate how biography involves navigating between the micro scale (details about her life) and the macro scale (Anishinaabe political practices and governance, as well as American settler-colonial political practices and governance). Collectively, her life showcases how Anishinaabe women’s involvement in the fur trade exemplifies deliberate political engagement aimed at strengthening her family and communities in the face of Anglo-American expansion.
Making the most of bioimaging data through interdisciplinary interactions
Authors: Uhlmann Virginie , Hartley Matthew , Moore Josh , Weisbart Erin , Zaritsky Assaf
Published: October 2024

The increasing technical complexity of all aspects involving bioimages, ranging from their acquisition to their analysis, has led to a diversification in the expertise of scientists engaged at the different stages of the discovery process. Although this diversity of profiles comes with the major challenge of establishing fruitful interdisciplinary collaboration, such collaboration also offers a superb opportunity for scientific discovery. In this Perspective, we review the different actors within the bioimaging research universe and identify the primary obstacles that hinder their interactions. We advocate that data sharing, which lies at the heart of innovation, is finally within reach after decades of being viewed as next to impossible in bioimaging. Building on recent community efforts, we propose actions to consolidate the development of a truly interdisciplinary bioimaging culture based on open data exchange and highlight the promising outlook of bioimaging as an example of multidisciplinary scientific endeavour.
The dual Ras-association domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis
Authors: McParland Emily D. , Gurley Noah J. , Wolfsberg Leah R. , Butcher T. Amber , Bhattarai Abhi , Jensen Corbin C. , Johnson Ruth I. , Slep Kevin C. , Peifer Mark
Published: October 2024

During development cells must change shape and move without disrupting dynamic tissue architecture. This requires robust linkage of cell–cell adherens junctions to the force-generating actomyosin cytoskeleton. Drosophila Canoe and mammalian afadin play key roles in the regulation of such linkages. One central task for the field is defining mechanisms by which upstream inputs from Ras-family GTPases regulate Canoe and afadin. These proteins are unusual in sharing two tandem Ras-association (RA) domains – RA1 and RA2 – which when deleted virtually eliminate Canoe function. Work in vitro has suggested that RA1 and RA2 differ in GTPase affinity, but their individual functions in vivo remain unknown. Combining bioinformatic and biochemical approaches, we find that both RA1 and RA2 bind to active Rap1 with similar affinities, and that their conserved N-terminal extensions enhance binding. We created Drosophila canoe mutants to test RA1 and RA2 function in vivo. Despite their similar affinities for Rap1, RA1 and RA2 play strikingly different roles. Deleting RA1 virtually eliminates Canoe function, whereas mutants lacking RA2 are viable and fertile but have defects in junctional reinforcement in embryos and during pupal eye development. These data significantly expand our understanding of the regulation of adherens junction–cytoskeletal linkages.
Innovative use of depth data to estimate energy intake and expenditure in Adélie penguins
Authors: Dupuis Benjamin , Kato Akiko , Hicks Olivia , Wisniewska Danuta M. , Marciau Coline , Angelier Frederic , Ropert-Coudert Yan , Chimienti Marianna
Published: October 2024

Energy governs species' life histories and pace of living, requiring individuals to make trade-offs. However, measuring energetic parameters in the wild is challenging, often resulting in data collected from heterogeneous sources. This complicates comprehensive analysis and hampers transferability within and across case studies. We present a novel framework, combining information obtained from eco-physiology and biologging techniques, to estimate both energy expenditure and intake in 48 Adélie penguins (Pygoscelis adeliae) during the chick-rearing stage. We employed the machine learning algorithm random forest (RF) to predict accelerometry-derived metrics for feeding behaviour using depth data (our proxy for energy acquisition). We also built a time-activity model calibrated with doubly labelled water data to estimate energy expenditure. Using depth-derived time spent diving and amount of vertical movement in the sub-surface phase, we accurately predicted energy expenditure. Movement metrics derived from the RF algorithm deployed on depth data were able to accurately detect the same feeding behaviour predicted from accelerometry. The RF predicted accelerometry-estimated time spent feeding more accurately compared with historical proxies such as number of undulations or dive bottom duration. The proposed framework is accurate, reliable and simple to implement on data from biologging technology widely used on marine species. It enables coupling energy intake and expenditure, which is crucial to further assess individual trade-offs. Our work allows us to revisit historical data, to study how long-term environmental changes affect animal energetics.