bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biotics and bacterial function: impact on gut and host health
Authors: Kandari Anwar , Odat Ma’en Al , Alzaid Fawaz , Scott Karen P 
Published: November 2024

Abstract
The human gut microbiota, the vast community of microbes inhabiting the gastrointestinal tract, plays a pivotal role in maintaining health. Bacteria are the most abundant organism, and the composition of bacterial communities is strongly influenced by diet. Gut bacteria can degrade complex dietary carbohydrates to produce bioactive compounds such as short-chain fatty acids. Such products influence health, by acting on systemic metabolism, or by virtue of anti-inflammatory or anti-carcinogenic properties. The composition of gut bacteria can be altered through overgrowth of enteropathogens (e.g. Campylobacter, Salmonella spp.), leading to dysbiosis of the gut ecosystem, with some species thriving under the altered conditions whereas others decline. Various “biotics” strategies, including prebiotics, probiotics, synbiotics, and postbiotics, contribute to re-establishing balance within the gut microbial ecosystem conferring health benefits. Prebiotics enhance growth of beneficial members of the resident microbial community and can thus prevent pathogen growth by competitive exclusion. Specific probiotics can actively inhibit the growth of pathogens, either through the production of bacteriocins or simply by reducing the gastrointestinal pH making conditions less favorable for pathogen growth. This review discusses the importance of a balanced gut ecosystem, and strategies to maintain it that contribute to human health.
Impact of a hub-and-spoke approach to hospital antimicrobial stewardship programmes on antibiotic use in Zambia
Authors: Kalungia Aubrey Chichonyi , Kampamba Martin , Banda David , Bambala Andrew Munkuli , Marshall Sarah , Newport Melanie , Clair-Jones Anja St , Alutuli Luke , Chambula Elias , Munsaka Lucky , Hamachila Audrey , Mwila Chiluba , Chanda Duncan , Chizimu Joseph , Chilengi Roma , Okorie Michael 
Published: November 2024

Abstract

Background
Antimicrobial stewardship programmes (ASPs) aim to optimize antibiotic use and prevent antimicrobial resistance.

Objective
This study assessed the impact of ASPs, initiated using a hub-and-spoke approach, on antibiotic use in Zambian public hospitals.

Methods
A pre–post study was conducted in 10 ASP-naive hospitals across Zambia using the Centers for Disease Control and Prevention (CDC)’s hospital-based ASP core elements (i.e. leadership, accountability, pharmacy expertise, stewardship actions, tracking progress, reporting and education) checklist and the global point prevalence survey methodology. The intervention involved technical staff from a national ‘hub’ hospital with an established ASP providing on-site orientation and mentorship to multidisciplinary teams of healthcare workers at 10 ‘spoke’ hospitals to build capacity in antimicrobial stewardship. ASP core elements and inpatient antibiotic use prevalence (AUP) were assessed before and 12 months after ASP implementation. Data were statistically analysed.

Results
The adoption of ASP core elements improved significantly (P = 0.001, 95% CI: −17.8 to −5.42). AUP decreased from 50.1% (±5.8, n = 1477) to 44.3% (±4.6, n = 1400) after 12 months, though the reduction was not statistically significant (P = 0.442; 95% CI: −9.8 to 21.6), with ‘Watch’ list antibiotics remaining the most commonly prescribed across the hospitals.

Conclusions
The hub-and-spoke approach successfully catalysed ASPs in public hospitals in Zambia, demonstrating the potential for improving antibiotic use practices over time, provided structural challenges are addressed. This approach and insights can guide stakeholders in Zambia and similar settings in enhancing hospital ASPs.
Unraveling Uncertainty: The Impact of Biological and Analytical Variation on the Prediction Uncertainty of Categorical Prediction Models
Authors: Martens Remy J H , van Doorn William P T M , Leers Mathie P G , Meex Steven J R , Helmich Floris 
Published: November 2024

Abstract

Background
Interest in prediction models, including machine learning (ML) models, based on laboratory data has increased tremendously. Uncertainty in laboratory measurements and predictions based on such data are inherently intertwined. This study developed a framework for assessing the impact of biological and analytical variation on the prediction uncertainty of categorical prediction models.

Methods
Practical application was demonstrated for the prediction of renal function loss (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) and 31-day mortality (advanced ML model) in 6360 emergency department patients. Model outcome was calculated in 100 000 simulations of variation in laboratory parameters. Subsequently, the percentage of discordant predictions was calculated with the original prediction as reference. Simulations were repeated assuming increasing levels of analytical variation.

Results
For the ML model, area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity were 0.90, 0.44, and 0.96, respectively. At base analytical variation, the median [2.5th–97.5th percentiles] percentage of discordant predictions was 0% [0%–28.8%]. In addition, 7.2% of patients had &gt;5% discordant predictions. At 6× base analytical variation, the median [2.5th–97.5th percentiles] percentage of discordant predictions was 0% [0%–38.8%]. In addition, 11.7% of patients had &gt;5% discordant predictions. However, the impact of analytical variation was limited compared with biological variation. AUROC, sensitivity, and specificity were not affected by variation in laboratory parameters.

Conclusions
The impact of biological and analytical variation on the prediction uncertainty of categorical prediction models, including ML models, can be estimated by the occurrence of discordant predictions in a simulation model. Nevertheless, discordant predictions at the individual level do not necessarily affect model performance at the population level.
Cecal metabolomics of 2 divergently selected rabbit lines revealed microbial mechanisms correlated to intramuscular fat deposition
Authors: Zubiri-Gaitán Agostina , Martínez-Álvaro Marina , Blasco Agustín , Hernández Pilar 
Published: November 2024

Abstract
The gastrointestinal microbiota plays a key role in the host physiology and health through a complex host–microbiota co-metabolism. Metabolites produced by microbial metabolism can travel through the bloodstream to reach distal organs and affect their function, ultimately influencing the development of relevant production traits such as meat quality. Meat quality is a complex trait made up of a number of characteristics and intramuscular fat content (IMF) is considered to be one of the most important parameters. In this study, 52 rabbits from 2 lines divergently selected for IMF (high-IMF (H) and low-IMF (L) lines) were used to perform an untargeted metabolomic analysis of their cecal content, with the aim to obtain information on genetically determined microbial metabolism related to IMF. A large, correlated response to selection was found in their cecal metabolome composition. Partial least squares discriminant analysis was used to identify the pathways differentiating the lines, which showed a classification accuracy of 99%. On the other hand, 2 linear partial least squares analyses were performed, one for each line, to extract evidence on the specific pathways associated with IMF deposition within each line, which showed predictive abilities (estimated using the Q2) of approximately 60%. The most relevant pathways differentiating the lines were those related to amino acids (aromatic, branched-chain, and gamma-glutamyl), secondary bile acids, and purines. The higher content of secondary bile acids in the L-line was related to greater lipid absorption, while the differences found in purines suggested different fermentation activities, which could be related to greater nitrogen utilization and energy efficiency in the L-line. The linear analyses showed that lipid metabolism had a greater relative importance for IMF deposition in the L-line, whereas a more complex microbial metabolism was associated with the H-line. The lysophospholipids and gamma-glutamyl amino acids were associated with IMF in both lines; the nucleotide and secondary bile acid metabolisms were mostly associated in the H-line; and the long-chain and branched-chain fatty acids were mostly associated in the L-line. A metabolic signature consisting of 2 secondary bile acids and 2 protein metabolites was found with 88% classification accuracy, pointing to the interaction between lipid absorption and protein metabolism as a relevant driver of the microbiome activity influencing IMF.
Modeling of skeletal development and diseases using human pluripotent stem cells
Authors: Hojo Hironori , Tani Shoichiro , Ohba Shinsuke 
Published: November 2024

Abstract
Human skeletal elements are formed from distinct origins at distinct positions of the embryo. For example, the neural crest produces the facial bones, the paraxial mesoderm produces the axial skeleton, and the lateral plate mesoderm produces the appendicular skeleton. During skeletal development, different combinations of signaling pathways are coordinated from distinct origins during the sequential developmental stages. Models for human skeletal development have been established using human pluripotent stem cells (hPSCs) and by exploiting our understanding of skeletal development. Stepwise protocols for generating skeletal cells from different origins have been designed to mimic developmental trails. Recently, organoid methods have allowed the multicellular organization of skeletal cell types to recapitulate complicated skeletal development and metabolism. Similarly, several genetic diseases of the skeleton have been modeled using patient-derived induced pluripotent stem cells and genome-editing technologies. Model-based drug screening is a powerful tool for identifying drug candidates. This review briefly summarizes our current understanding of the embryonic development of skeletal tissues and introduces the current state-of-the-art hPSC methods for recapitulating skeletal development, metabolism, and diseases. We also discuss the current limitations and future perspectives for applications of the hPSC-based modeling system in precision medicine in this research field.
Heat transfer and entropy generation analysis of ternary nanofluid
Authors: Liang Ruishi , Hanif Hanifa , Song Jie , Alzahrani S S 
Published: November 2024

Abstract
In light of the rising demand for improved heat transfer in thermal systems, this work offers a unique technique for boosting heat transfer capacity and reducing entropy generation using a ternary nanofluid. Moreover, constant pressure gradient, magnetic field, Joule heating, and thermal radiation also contribute to the flow dynamics. The 2D mathematical model is solved numerically using a finite difference method and the simulations are done in MATLAB. The obtained results show that ternary nanoparticles not only increase the thermal rates but are also helpful in maintaining the irreversibility of a system. It is also observed that the heat transfer of the base fluid increased by 7.5%, 8.3%, and 8.5% on adding TiO$_2$, CuO$-$TiO$_2$, and MgO$-$CuO$-$TiO$_2$ nanoparticles, respectively.
Left Atheist Activism and Crime of Genocide in Francoist Spain
Authors: Kazyrytski Leanid 
Published: November 2024

Abstract
This article examines whether the mass killings of people with leftist ideology by the Franco regime can be interpreted as genocide in accordance with the provisions of international law. The present study underscores the influence of religion on the configuration of Francoist criminal policy and provides evidence that allows Francoist repression to be considered as genocide. Individuals with leftist ideologies were presented not only as a political group but also as a religious group with atheist and non-Catholic beliefs. In this sense, the mass political repression conducted by the Franco regime fulfils the objective elements (actus reus) of genocide due to the fact the religious element played a significant role in justifying the annihilation of Republicans. The victims of Francoist repression were in fact selected not only because they belonged to a certain political movement or party but also because they belonged to a certain religious group.
Low-dose add-on methadone for cancer pain management: a retrospective analysis of 102 Japanese patients
Authors: Sato Tetsumi , Fukutomi Akira , Kawamura Taiichi , Kawakami Kyohei , Sato Tetsu , Kamo Yoshiko , Suzuki Tomomi , Hagiya Shota , Tanaka Rei 
Published: November 2024

Abstract

Background
Methadone was introduced in 2013 for the treatment of intractable cancer pain in Japan and is indicated for patients receiving opioid doses ≧60 mg/day as an oral morphine equivalent. Low-dose (≦10 mg/day) add-on methadone to prior opioids has been reported from European countries to successfully relieve various types of intractable cancer pain; however, there are few reports of such use in Japan. The aim of this study was to analyze more than a hundred cases with low-dose add-on methadone to treat intractable pain in Japanese cancer patients.

Methods
All cases in which 5 or 10 mg/day of methadone was added to prior opioids by the Palliative Care Team or Division of Palliative Medicine in our hospital during the period between April 2016 and September 2023 were extracted and analyzed retrospectively on electrical medical charts.

Results and conclusions
A total of 102 cases were extracted with a male-to-female ratio of 60:42, and the age (mean ± SD) was 62.8 ± 14.7 years old. Methadone was introduced in an inpatient setting to 86 patients. The major pathologies that caused intractable pain were spinal metastases in 48, pelvis or pelvic floor lesions in 29 and pleural and/or chest wall lesions in 16. The most common mechanism of pain was the mixture of somatic and neuropathic components. The major opioids administered prior to methadone included tapentadol in 46 patients, hydromorphone in 36 and oxycodone in 19. The dose of the prior opioids [median, (interquartile range: IQR)] was 97, (62.8–167.3) (range: 15–1313) mg/day of oral morphine equivalent. Radiotherapy, chemotherapy and nerve blocks were performed as concomitant therapies in 48, 22 and 11 patients, respectively (with some overlap). The number of rescue doses [median (IQR)] was significantly decreased from three (two to five) on the day before methadone to one (zero to four) after seven days from methadone initiation. The side effects leading to discontinuation of methadone were drowsiness in three cases, nausea in three cases and dizziness in one case (with some overlap). Compared with complete switching from other opioids, low-dose add-on methadone can reduce the possibility of major dose discrepancies and can be quickly adjusted by combined opioid reduction/increase. Low-dose add-on methadone can be an effective and safe method for intractable cancer pain.
Awareness and implementation of comprehensive genomic profiling and cancer support for adolescents and young adults among healthcare professionals in Osaka, Japan
Authors: Nishida Tsutomu , Miyamoto Miwa , Yasuda Junko , Ninomiya Yukie , Kosugi Satoru , Mizuki Masao , Eguchi Hidetoshi , Imamura Hiroshi 
Published: November 2024

Abstract

Background
Comprehensive genomic profiling (CGP) and specialized support for adolescent and young adult (AYA) cancer patients are crucial yet underexplored areas of healthcare in Japan. This study investigated awareness of CGP testing and support for AYA cancer patients among healthcare professionals in Osaka.

Methods
An anonymous online survey was conducted from 31 January to 31 March 2024. The survey targeted all staff, including doctors, nurses, technicians, pharmacists and others, from eight Toyono Medical Area Cancer Medical Network Council hospitals. The survey included questions on basic demographics, awareness of CGP testing and support provided to patients with AYA cancer.

Results
Among the 720 respondents, 41.9% were aware of CGP testing, while 20.3% were unaware. Regarding AYA cancer, 60.7% were aware and 14.3% were unaware. Only 7.5% had frequent contact with AYA patients and 96.8% recognized the need for education and information. Awareness of CGP was greater among doctors (72.5%) than among other professionals (34.4%); similarly, AYA cancer awareness was higher among doctors (73.9%) than among other professionals (57.7%). CGP awareness among doctors varied by years of experience and institutional type, being highest in core and cooperative hospitals (80 and 78.6%, respectively) and among doctors with more than 21 years of experience (90%).

Conclusions
This study reveals significant gaps in CGP and AYA cancer awareness among healthcare professionals in Osaka, Japan, with doctors demonstrating higher awareness levels than other professionals. There is a pressing need for targeted educational programs to enhance the understanding and implementation of CGP and support AYA cancer patients.
Some or Other: Partitive Disanaphors Across Languages
Authors: Kapitonov Ivan , Bowler Margit 
Published: November 2024

Abstract
We present a cross-linguistically robust pattern of polyfunctionality between indefinite, partitive, and disanaphoric (‘another’) use of a single lexical item. In examining the connection between these different uses, we argue that a uniform semantics underlies all of them. We employ the salience theory of definiteness, with the specific implementation in a dynamic semantics with choice functions, to model the full spectrum of the attested uses without invoking implicit variables. The core meaning is the partitive implication, whereas the indefinite and the discourse-familiar disanaphoric readings are underspecified in the semantics and are argued to be additional construals conditioned by discourse factors. The partitive meaning, however, is shown itself to be subject to variable pragmatic packaging across languages, from being a part of the truth conditions to a postsupposition.
Redo phalloplasty and/or urethraplasty after previous flap failure in phalloplasty in transgender men: surgical considerations and outcomes
Authors: van der Sluis Wouter B , Al-Tamimi Muhammed , Pigot Garry L S , Buncamper Marlon , Smit Jan Maerten , van de Grift Tim C , Mullender Margriet G , Bouman Mark-Bram 
Published: November 2024

Abstract

Background
Primary phalloplasty in transgender men can be performed using a single or double free or pedicled flap to reconstruct the shaft and, if desired, the urethra. Vascular complications may result in total or partial loss of the used flap(s). Surgical management after flap loss in primary phalloplasty presents a challenge to the reconstructive surgeon.

Aim
To describe our experience with surgical reconstructive management after primary phalloplasty flap loss in transgender men and report on the clinical and participant-reported outcomes.

Methods
All transgender men who underwent a secondary reconstructive procedure after failure of the primary procedure between January 1989 and December 2023, at our institution, were identified. A retrospective chart review was conducted, recording relevant demographic and clinical data. In addition, participants were invited to complete a non-validated questionnaire consisting of questions regarding surgical outcomes, (sexual) functionality, and sexuality.

Outcomes
Surgical outcomes, flap failure, and self-reported outcomes.

Results
Eighteen individuals were included in this study, who underwent flap reconstruction of the phalloplasty shaft (n = 7), the urethra (n = 4), or both (n = 7). Primary phalloplasty was performed with urethral lengthening (UL) in 16 (89%) and without in 2 (11%). There were no redo phalloplasty flap failures. In those with UL 13/16 (81%) were able to void while standing. Eleven individuals completed the follow-up questionnaire. Most participants were “satisfied” (45%) or “very satisfied” (27%) with the appearance of their penis. All participants (strongly) agreed that when looking back, they would undergo the surgery all over again.

Clinical implications
Practical surgical tips, deducted from our experiences, are provided for gender surgeons performing (revision) phalloplasty and urethroplasty.

Strengths and Limitations
Strengths are the unique set of surgical reconstruction cases that has taught us valuable lessons. Data from this study can be used to optimize pre-operative counseling regarding flap loss complications and the outcomes of the subsequent management. Weaknesses comprise the retrospective nature, the low number of included individuals, and use of non-validated questionnaires for self-reported outcomes.

Conclusion
Flap loss after primary phalloplasty in transgender men is a serious complication. Successful secondary reconstruction of the phalloplasty can be performed using a new pedicled or free flap.
Modified calculation of the IIEF6—a more accurate assessment of erectile function in middle-aged men
Authors: Kirchhoff Florian P , Hübner Rebekka D , Kron Martina , Schiele Stefan , Schulwitz Helga , Peter Cornelia , Meissner Valentin H , Jahnen Matthias , Gschwend Jürgen E , Herkommer Kathleen 
Published: November 2024

Abstract

Background
The Erectile Function Domain of the International Index of Erectile Function (IIEF6) is inaccurate in assessing erectile function in men who are not practicing sexual intercourse. Improvement through a modification was recently tested on patients after radical prostatectomy. This study examines the application of this modification in a population-based cohort of middle-aged men.

Aim
To assess the feasibility of a modified IIEF6 in a population-based random sample of 50-year old men in Germany.

Methods
4924 men were included. IIEF6, Erection Hardness Score (EHS), and causes for the absence of sexual intercourse within the previous 4 weeks were assessed. Modified calculation (double weighting of non-intercourse IIEF6 questions) was applied in case of absence due to external circumstances.

Outcomes
Impact of the modification on erectile dysfunction (ED) prevalence and agreement between IIEF6 and EHS in ED classification.

Results
As a result of the modified calculation, ED prevalence in the overall study sample decreased by 6.2% to a rate of 27.2%. Agreement between IIEF6 and EHS was increased from 2.7% to 73.4% in men with no sexual intercourse due to external circumstances.

Clinical Implications
An additional inquiry into the reason for the absence of sexual intercourse and modified calculation enhances the accuracy of IIEF6 in evaluating erectile function of the individual man.

Strengths and Limitations
This study comprises a large population-based sample. As the study population was exclusively 50-year-old men, results may not be representative of the population average.

Conclusion
A more accurate evaluation of an individual man’s erectile function may be achieved by using a modified version of the IIEF6.