bluuebunny/crossref_metadata_2025 huggingface dataset:
Real world study of GLP-1 receptor agonists in overweight or obese type 2 diabetes by using repeated measurement analysis of variance
Authors: Yang Wanying , Zhou Xiangming , Miao Yuanyuan , Wang Lu , Zhao Yunhui , Ke Tingyu , Ban Lili
Published: August 2024

To investigate the safety and efficacy of long-acting glucagon like peptide-1 receptor agonists in overweight or obese patients with type 2 diabetes. Overweight or obese patients with type 2 diabetes from July 2021 to June 2022 were randomly divided into control group (metformin) and experimental group (metformin + dulaglitide or semaglutide). Repeated measures analysis of variance was used to compare Hemoglobin A1c, fasting plasma glucose and body mass index (BMI) of patients before treatment, 6 months and 12 months after treatment. The adverse reactions of patients before treatment and 12 months after treatment were analyzed. The time effect of Hemoglobin A1c, fasting plasma glucose and BMI in the control group (n = 35) and the experimental group (n = 32) were statistically significant (P < .001), and the intergroup effect of BMI was statistically significant (P < .05). The interaction effect of BMI was statistically significant (P < .001). The BMI level of the experimental group was lower than that of the control group at 6 and 12 months after treatment (P < .001). There was no significant difference in the incidence of adverse reactions between the 2 groups (P > .05). Long-acting glucagon like peptide-1 receptor agonists, such as dulaglitide and semaglutide, not only reduce glycosylated hemoglobin levels, but also significantly improve BMI in overweight or obese patients with type 2 diabetes.
Effects of 6-month administration of tofogliflozin on cardiac function in elderly patients with heart failure with preserved ejection fraction: A retrospective study of a patient cohort
Authors: Higashikawa Toshihiro , Ito Tomohiko , Mizuno Takuro , Ishigami Keiichirou , Kuroki Kengo , Haraguchi Takatoshi , Yamada Shinya , Sangen Ryusho , Kiyosawa Jun , Saito Atsushi , Iguchi Masaharu , Nakahashi Takeshi , Kasamaki Yuji , Fukuda Akihiro , Kanda Tsugiyasu , Okuro Masashi
Published: August 2024

Patients with type 2 diabetes mellitus are frequently hospitalized for heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e’), measured by echocardiography, is a simple and convenient indicator of diastolic dysfunction. Various large clinical trials have reported that sodium glucose transporter-2 inhibitor therapy reduced cardiovascular events and hospitalizations in heart failure patients. We examined the effect of tofogliflozin on various physiological and cardiac function. A retrospective analysis was performed on elderly patients aged 65 years or older with type 2 diabetes mellitus attending Himi Municipal Hospital who were taking oral tofogliflozin 20 mg/day. Measurement of physiological and hormonal variables, blood sampling, and echocardiographic evaluations at 0, 1, 3, and 6 months were performed on those with ejection fraction (EF) of 40% or greater at the time of treatment. Statistical analysis was performed using t-tests and mixed-effects models, with brain natriuretic peptide less than or not less than 100 pg/mL, estimated glomerular filtration rate (eGFR) less than or not less than 50 mL/min/1.73 m2, and diuretics administered or not. Hypoglycemic effects were observed at 0, 1, 3, and 6 months. At each time point, EF was retained and E/e’ was significantly reduced. On the other hand, most physiological parameters and laboratory results showed no clinical abnormalities. Mixed-effects models showed time-dependent reduction of E/e’ in high/low brain natriuretic peptide, high/low eGFR, with or without diuretics between baseline and at 6 months. The interaction with time was significant in high/low eGFR. Tofogliflozin was shown to improve E/e’, a measure of diastolic function, while maintaining EF, with hypoglycemic effects and no clinical side effects.
Efficacy and safety of peroral endoscopic myotomy for pediatric achalasia: A nationwide study
Authors: Luvsandagva Bayasgalan , Adyasuren Battulga , Bagachoimbol Bayaraa , Luuzanbadam Ganbayar , Bai Tao , Jalbuu Narantsatsralt , Duger Davaadorj , Hou Xiaohua
Published: August 2024

Achalasia, a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and loss of esophageal peristalsis, significantly impacts pediatric patient quality of life through symptoms like dysphagia, chest pain, and weight loss. This nationwide retrospective cohort study evaluates the efficacy and safety of peroral endoscopic myotomy (POEM) for pediatric achalasia in Mongolia, contributing to the limited global data on this minimally invasive treatment in children. Conducted between February 2020 and March 2022 at 2 tertiary centers, the study included symptomatic achalasia patients, treatment-naive or those with unsatisfactory outcomes from previous esophageal dilations. The POEM procedure was assessed for its impact on esophageal structure and function, symptom severity via the Eckardt score, and procedure-related safety, with outcomes measured at baseline, 3 days, and 12 months post-procedure. The study demonstrated notable post-procedure improvements across all measured outcomes: abnormal contraction length and esophageal width significantly reduced, underscoring the procedure’s effectiveness. More precisely, the integrated relaxation pressure showed a significant improvement from a mean of 26.8 mm Hg (standard deviation [SD], 5.4 mm Hg) pre-procedure to 10.8 mm Hg (SD, 1.1 mm Hg) 12 months (P < .001). Similarly, Eckardt scores, which assess symptom severity, improved significantly from a pre-procedure mean of 7.0 (SD, 1.0) to a substantially lower score post-procedure (P < .001), reflecting enhanced patient quality of life and symptom alleviation. This study underscores POEM’s role as an effective, minimally invasive option for pediatric achalasia management within the Mongolian population, offering significant symptomatic relief and improved esophageal function.
A CARE-compliant article: A case report of retroperitoneal endometrial stromal sarcoma with multiple pulmonary metastases and literature review
Authors: Fang Yaoyao , Zhou Xiaoli , Bai Jing , Lin Qiuju , Zheng Yingchun , Bo Sijia , Sui Lei , Zhu Ting , Bai Nuo , Sun Li
Published: August 2024

Rationale:

Endometrial stromal sarcoma is an extremely rare mesenchymal neoplasm occurring in the extrauterine. Retroperitoneal endometrial stromal sarcoma with multiple pulmonary metastases, in particular, is extremely rare.

Patient concerns:

Forty-seven-year-old woman (gravida 3, para 2), was referred to our institution with complaints of fever.

Diagnoses:

Ultrasound and computed tomographic imaging of the abdomen identified the presence of masses in the pelvic region. Additionally, computed tomographic scans and X-ray evaluations of the thorax detected dispersed masses in both the lungs and pelvic area. Histopathological analysis of the pelvic region indicated the presence of low-grade endometrial stromal sarcoma. A computed tomography-guided pneumocentesis was conducted to further characterize the pulmonary lesions, confirming the diagnosis of low-grade endometrial stromal sarcoma.

Interventions:

The patient underwent tumor resection, subsequent treatment with Medroxyprogesterone acetate for 6 months, received microwave ablation for multiple lung metastases, PARP1 inhibitor for 4 courses, and has been undergoing chemotherapy (epirubicin/ifosfamide) up to the present time.

Outcomes:

Partial remission was obtained after the above treatment and this patient is now still alive maintaining for 3 years.

Lessons:

The identification and management of this disease remain a significant challenge due to its low prevalence. Further research involving a larger number of cases is necessary to ensure consistency in diagnosis and to establish effective treatment guidelines.
Levothyroxine sodium tablets reversed Hashimoto thyroiditis-induced kidney injury, muscle injury, and lipid metabolism disorder: A case report and literature review
Authors: Li Xuesong , Cao Chenxiang
Published: August 2024

Rationale:

Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed.

Patient concerns, Diagnoses, and Interventions:

We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate).

Outcomes and Lessons:

Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms.
The role of geriatric assessment in the care of older adults undergoing urologic cancer surgery
Authors: Wingfield Sarah A.
Published: August 2024

Purpose of review

Older adults undergoing urologic cancer surgery have unique needs and require unique risk assessment and management. This review will discuss recent literature on brief screening tools to identify high risk older adults in the preoperative period and the role of comprehensive geriatric assessment (CGA) in identifying and addressing geriatric vulnerabilities for older adults undergoing urologic cancer surgery.

Recent findings

Frailty screening tools such as the G8 can be used to identify patients who are at an increased risk of adverse postoperative outcomes such as postoperative complications and prolonged length of stay. CGA can provide more detailed information about geriatric syndromes prior to urologic cancer surgery.

Screening tools for geriatric vulnerabilities and CGA are valuable tools for the urologist in identifying high-risk older adults, counseling patients on perioperative risk and addressing vulnerabilities prior to surgery. Making health system-wide changes can allow this optimal practice to reach more older surgical patients.
A Rare Complication in the Oral Local Infiltration Anesthesia
Authors: Yang Sisi , Zhou Hailing , Dai Yongbo
Published: August 2024

The present report describes a rare complication named Kuhn anemia, which happened during local infiltration anesthesia of maxillary wisdom tooth. A 24-year-old male was referred for residual crown of left maxillary wisdom tooth and therefore required extraction. Oral examination revealed a buccal impacted left maxillary wisdom tooth (28), severe caries affecting the dental pulp, and pain with percussion. This case was diagnosed as impacted wisdom tooth 28 and pulpitis. Thus, the authors performed an extraction of the 28. After injection of articaine hydrochloride (68 mg:1.7 mL) containing epinephrine (1:100,000) as local anesthetic, the patient felt pain and heat in the left cheek, and an irregularly shaped pale area appeared on the left cheek. The authors stopped the surgery and comforted him. After a 30-minute break, the cheek turned normal, and abnormal sensation was no longer felt.
Surgeon-Scientists Going Extinct
Authors: Pfister Matthias , Li Zhihao , Huwyler Florian , Tibbitt Mark W. , Puhan Milo A. , Clavien Pierre-Alain ,   the Research Sustainability Group
Published: August 2024

Objective:

To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies.

Background:

Surgeons who conduct research in addition to patient care are referred to as “surgeon-scientists.” While their value to society remains undisputed, their numbers and associated impact have been plunging. While reasons have been well identified along with proposals for countermeasures, their application has largely failed.

Methods:

We conducted a systematic review covering all aspects of surgeon-scientists together with a global online survey among 141 young academic surgeons. Using gap analysis, we determined implementation gaps for proposed measures. Then, we developed a comprehensive rescue package.

Results:

A surgeon-scientist must actively and continuously engage in both patient care and research. Competence in either field must be established through protected training and criteria of excellence, particularly reflecting contribution to innovation. The decline of surgeon-scientists has reached an unprecedented magnitude. Leadership turning hospitals into “profit factories” is one reason, a flawed selection process not exclusively based on excellence is another. Most importantly, the appreciation for the academic mission has vanished. Along with fundamentally addressing these root causes, surgeon-scientists’ path to excellence must be streamlined, and their continuous devotion to innovation cherished.

Conclusions:

The journey of the surgeon-scientist is at a crossroads. As a society, we either adapt and shift our priorities again towards innovation or capitulate to greed for profit, permanently losing these invaluable professionals. Successful rescue packages must not only involve hospitals and universities but also the political sphere.
Rewilding psychology
Authors: Baggs Edward , Sanches de Oliveira Guilherme
Published: August 2024

Some commentators have recently argued that scientific psychology is overly reliant on artificial laboratory-based activities and that it undervalues field-based investigations. However, it remains unclear how a field-based programme of psychological research might be organized in a scalable way. We examine and compare two existing field-based approaches: Roger Barker’s behaviour settings programme and Edwin Hutchins’s distributed cognition programme. Both programmes prioritize observational work, and both reject the individual as the unit of analysis in favour of a community-scale unit. However, whereas the behaviour settings programme is concerned with structural properties of community life, distributed cognition is concerned more narrowly with the functional analysis of expert team performance. We discuss how these programmes can inform a future community-scale approach to studying psychology in the wild. We conclude that the two programmes are proof of concept of the possibility of a scientific psychology that rejects methodological individualism.

This article is part of the theme issue ‘People, places, things and communities: expanding behaviour settings theory in the twenty-first century’.
Navigating the normativity of behaviour settings: an observational case study
Authors: Di Rienzo Giulia , Myin Erik , van Dijk Ludger
Published: August 2024

Traditionally, sensitivity to situational norms is understood as deriving from internal cognitive states that represent the rules for appropriate conduct. On an alternative view, norms are ‘out there’, in the practices and situations themselves, without being duplicated in the head. However, what does normativity look like when it is performed by people engaging with a concrete situation? A ‘behaviour setting’ offers a window onto these dynamics. This article presents an observational case study of normative coordination within a behaviour setting. Immersed in a scientific laboratory setting, the observations show how the normative demands of the overall behaviour setting can give shape to various places of action, or ‘synomorphs’, which invite the participants’ activities. Responding to the different needs of each synomorph, in turn, maintains the behaviour setting. What connects these two reciprocal timescales of activity are the situationally sensitive activities of the participants. We end with several examples that bring such sensitivity to the interdependence of the norms of a behaviour setting to the fore.

This article is part of the theme issue ‘People, places, things, and communities: expanding behaviour settings theory in the twenty-first century’.
Individualized Hybrid Electroconvulsive Therapy (i-HECT) Shows Rapid Anti-Depressant Effect and Improved Cognition in Young Patients with Depression
Authors: Zhang Jing-ya , Zeng Lun , Li Jia , Chen Mian-mian , Xu Shu-xian , Tan Baijian , Xie Xin-hui
Published: August 2024

Background

For young patients with depression, electroconvulsive therapy (ECT) is highly effective but causes acute cognitive side effects. We designed a new i-HECT therapy combines ECT with low-charge electrotherapy (LCE) and individual symptom monitoring to reduce cognitive impairments.

Methods

i-HECT comprised two treatments: ECT and LCE. ECT utilized an energy set of 1.5 times the seizure threshold (ST), while LCE was set at 0.5 ST. The initial session employed ECT. Subsequent sessions involved ECT or LCE, depending on whether meeting the ECT-LCE transition criteria (MADRS total score < 22 or ≥ 50% reduction), assessed after each session.

Results

The intention-to-treat analysis revealed an 80.4% response rate and a 58.7% remission rate (Hedges’ g = 3.29). Notably, both subjective and objective cognitive functions significantly improved post-i-HECT treatments and during the 3-month follow-up periods.

Conclusion

The i-HECT protocol may provide a rapid antidepressant treatment option with cognitive benefits for young depression patients.

Highlights

Designed a novel but simple ECT protocol, i-HECT, for young depression patients.

The trial employed Simon’s optimal two-stage design with a high power of 0.95.

The i-HECT rapidly improved both depression symptoms and cognitive functions.
Genetic estimates and genome-wide association studies of antibody response in Tanzanian dairy cattle
Authors: Hernandez-Castro Luis E , Cook Elizabeth Anne Jessie , Matika Oswald , Mengele Isaac Joseph , Motto Shabani Kiyabo , Bwatota Shedrack Festo , Zirra-Shallangwa Bibiana , Pong-Wong Ricardo , Prendergast James , Mrode Raphael , Toye Philip G. , Komwihangilo Daniel Mushumbusi , Lyatuu Eliamoni , Karani Benedict E. , Nangekhe Getrude , Mwai Okeyo Ally , Shirima Gabriel Mkilema , de Clare Bronsvoort Barend Mark
Published: August 2024

Identifying the genetic determinants of host defence against infectious pathogens is central to enhancing disease resilience and therapeutic efficacy in livestock. Here we have taken a genome-wide association approach to identify genetic variants associated with the presence of serological markers for important infectious diseases affecting dairy cattle in smallholder farms. Assessing 668,911 single-nucleotide polymorphisms in 1977 crossbreed cattle sampled from six regions of Tanzania, we identified high levels of interregional admixture and European introgression which may increase infectious disease susceptibility relative to indigenous breeds. Heritability estimates ranged from 0.03 (SE ± 0.06) to 0.44 (SE ± 0.07) depending on the pathogen assayed. Preliminary genome scans revealed several loci associated with seropositivity to the viral diseases Rift Valley fever and bovine viral diarrhoea, the protozoan parasitesNeospora caninumandToxoplasma gondii, and the bacterial pathogensBrucella sp, Leptospira hardjoandCoxiella burnetti. The associated loci mapped to genes involved in immune defence, tumour suppression, neurological processes, and cell exocytosis. We discuss future work to clarify the cellular pathways contributing to general and taxon-specific infection responses and to advance selective breeding and therapeutic target designs.
Role of SCAL1 in Modulating Oxidative Stress, Cancer Stemness, Apoptotic Resistance in Tumorigenic Differentiation of Cigarette Smoke-Exposed BEAS-2B Cells
Authors: Sengupta Debmalya , Banerjee Souradeep , Sengupta Mainak
Published: August 2024

The smoke and cancer-associated lncRNA 1 (SCAL1) is an emergent biomarker in lung cancer. However, the precise role of SCAL1 as a mediator of tobacco smoke-induced lung carcinogenesis remains unclear. BEAS-2B cells were cultured and exposed to 20% cigarette smoke extract (CSE), followed by quantification of SCAL1. We evaluated the impact of SCAL1 on cell viability, ROS mitigation, cancer stemness, tumorigenic differentiation, cellular invasiveness, and apoptosis for different CSE incubation time points through SCAL1 expressional modulation using SCAL1-specific siRNAs and scrambled controls. We observed an upregulation of SCAL1 in cells exposed to CSE for 2, 4, and 6 hours, with the highest expression observed at 6 hours (p<0.001). Exposure of BEAS-2B cells to CSE showed the formation of focal adhesions and stress fibers resembling tunneling nanotubes. Intracellular ROS levels significantly increased upon CSE exposure compared to control cells (p<0.05). We found increased levels of anti-apoptotic and cancer stem (CSC) cell markers like BCL2, ALDH1A1, CD133, CD44, and TCTP and decreased levels of TP53 in CSE-exposed cells. Knockdown of SCAL1 using siRNA transfection reversed these effects at all time points. Additionally, we observed a significant decrease in the number of spheroid colonies in siSCAL1 (+) cells compared to siSCAL1 (-) cells (p<0.01) exposed to CSE. SCAL1 is pivotal in mediating cellular responses to cigarette smoke, leading to tumorigenic differentiation of BEAS-2B cells. Understanding the mechanisms could provide valuable insights into lung cancer pathogenesis and therapeutic approaches.
LongReadSum: A fast and flexible quality control and signal summarization tool for long-read sequencing data
Authors: Perdomo Jonathan Elliot , Ahsan Mian Umair , Liu Qian , Fang Li , Wang Kai
Published: August 2024

While several well-established quality control (QC) tools are available for short reads sequencing data, there is a general paucity of computational tools that provide long read metrics in a fast and comprehensive manner across all major sequencing platforms (such as PacBio, Oxford Nanopore, Illumina Complete Long Read) and data formats (such as ONT POD5, FAST5, basecall summary files and PacBio unaligned BAM). Additionally, none of the current tools provide support for summarizing Oxford Nanopore basecall signal or comprehensive base modification (methylation) information from genomic data. Furthermore, nowadays a single PromethION flowcell on the Oxford Nanopore platform can generate terabytes of signal data, which cannot be handled by existing tools designed for small-scale flowcells. To address these challenges, here we present LongReadSum, a multi-threaded C++ tool which provides fast and comprehensive QC reports on all major aspects of sequencing data (such as read, base, base quality, alignment, and base modification metrics) and produce basecalling signal intensity information from the Oxford Nanopore platform. We demonstrate use cases to analyze cDNA sequencing, direct mRNA sequencing, reduced representation methylation sequencing (RRMS) through adaptive sequencing, as well as whole genome sequencing (WGS) data using diverse long-read platforms.
A Dual-Fluorescence Assay for Gene Delivery Vehicle Screening in Macrophages with an Inflammation-Inducible Reporter Construct
Authors: Ivy Allie , Bess Shelby N , Agrawal Shilpi , Kochar Varun , Muldoon Timothy J , Nelson Christopher E.
Published: August 2024

Macrophages are a promising target for therapeutics in various applications such as regenerative medicine and immunotherapy for cancer. Due to their plastic nature, macrophages can switch from a non-activated state to activated with the smallest environmental change. For macrophages to be effective in their respective applications, screening for phenotypic changes is necessary to elucidate the cell response to different delivery vehicles, vaccines, small molecules, and other stimuli. We created a sensitive and dynamic high-throughput screening method for macrophages based on the activation of NF-κB. For this reporter, we placed an mCherry fluorescence gene under the control of an inflammatory promoter, which recruits NF-κB response elements to promote expression during the inflammatory response in macrophages. We characterized the inflammatory reporter based on key markers of an inflammatory response in macrophages including TNF-α cytokine release and immunostaining for inflammatory and non-inflammatory cell surface markers. With the inflammatory reporter, we also were able to create an LPS dose curve to determine the dynamic range of the reporter and determine the sensitivity of the reporter to stimulus through timepoint analysis of stimulus vs. non-stimulus treated reporter cells. We then used the reporter cell line to determine both delivery efficiency and inflammatory response to different viral and non-viral gene delivery vehicles. Thie screening technique developed here provides a dynamic, high-throughput screening technique for determining inflammatory response by mouse macrophages to specific stimuli and provides insight into the inflammatory response of mouse macrophages to different viral and non-viral gene delivery methods.
PeakClimber: A software tool for the accurate quantification of complex multianalyte HPLC chromatograms using the exponential Gaussian function
Authors: Derrick Joshua T. , Deme Pragney , Haughey Norman , Farber Steven A. , Ludington William B.
Published: August 2024

High-performance liquid chromatography (HPLC) is a common medium-throughput technique to quantify the components of often complex mixtures like those typically obtained from biological tissue extracts. However, analysis of HPLC data from complex multianalyte samples is hampered by a lack of tools to accurately determine the precise analyte quantities on a level of precision equivalent to mass-spectrometry approaches. To address this problem, we developed a tool we call PeakClimber, that uses a sum of exponential Gaussian functions to accurately deconvolve overlapping, multianalyte peaks in HPLC traces. Here we analytically show that HPLC peaks are well-fit by an exponential Gaussian function, that PeakClimber more accurately quantifies known peak areas than standard industry software for both HPLC and mass spectrometry applications, and that PeakClimber accurately quantifies differences in triglyceride abundances between colonized and germ-free fruit flies.
Spike-to-excite: photosensitive seizures in biologically-realistic spiking neural networks
Authors: Taylor Luke , Fasol Melissa Claire Maaike
Published: August 2024

Photosensitive Epilepsy (PE) is a neurological disorder characterized by seizures triggered by harmful visual stimuli, such as flashing lights and high-contrast patterns. The mechanisms underlying PE remain poorly understood, and to date, no computational model has captured the phenomena associated with this condition. Biologically detailed spiking networks trained for efficient prediction of natural scenes have been shown to capture V1-like characteristics. Here, we show that these models display seizure-like activity in response to harmful stimuli while retaining healthy responses to non-provocative stimuli when post-synaptic inhibitory connections are weakened. Notably, our adapted model resembles the motion tuning and contrast gain responses of excitatory V1 neurons in mice with optogenetically reduced inhibitory activity. We offer testable predictions underlying the pathophysiology of PE by exploring how reduced inhibition leads to seizure-like activity. Finally, we show that artificially injecting pulsating input current into the model units prevents seizure-like activity and restores baseline function. In summary, we present a model of PE that offers new insights to understand and treat this condition.
Parcellation of the primate prefrontal cortex by cognitive control operations
Authors: Wang Xuanyu , Hähnke Daniel , Nieder Andreas , Jacob Simon N.
Published: August 2024

Modular organization, the division of the cerebral cortex into functionally distinct subregions, is well established in the primate sensorimotor cortex, but debated in the cognitive association cortex, including the lateral prefrontal cortex (PFC). So far, single-unit recordings have not confirmed the prefrontal rostro-caudal gradients observed in neuroimaging and neuroanatomical experiments. To bridge these microscale and macroscale perspectives, we obtained microelectrode recordings with twice the spatial coverage of conventional studies from the PFC of monkeys engaged in a working memory task. Neighboring electrodes shared task-related neural dynamics that were stable across recording sessions and formed spatially continuous, mesoscale clusters with distinct local and long-range fronto-parietal connectivity. Spiking activity was cluster-specific and related to either the encoding, maintenance or decoding of working memory content. Our findings support parcellation of the PFC by cognitive control operations rather than by processed information, indicating that modularity is a fundamental architectural principle across the primate cortex.
Cryptic host phenotypic heterogeneity drives diversification of bacteriophage λ
Authors: De La Fuente Caesar A. , Lahoud Nehme , Meyer Justin R.
Published: August 2024

Bacteriophages, the most abundant and genetically diverse life forms, seemingly defy fundamental ecological theory by exhibiting greater diversity than their numerous bacterial prey. This paradox raises questions about the mechanisms underlying parasite diversity. To investigate this, we took advantage of a surprising experimental result: when bacteriophage λ is continually supplied a single host, λ repeatedly evolves multiple genotypes within the same flask that vary in their receptor use. Measurements of negative frequency-dependent selection between receptor specialists revealed that diversifying selection drove their evolution and maintenance. However, the source of environmental heterogeneity necessary to generate this type of selection was unclear, as only a single isogenic host was provided and replenished every eight hours. Our experiments showed that selection for different specialist phages oscillated over the 8-hour incubation period, mirroring oscillations in gene expression of λ’s two receptors (Escherichia coliouter membrane proteins LamB and OmpF). These receptor expression changes were attributed to both cell-to-cell variation in receptor expression and rapid bacterial evolution, which we documented using phenotypic resistance assays and population genome sequencing. Our findings suggest that cryptic phenotypic variation in hosts, arising from non-genetic phenotypic heterogeneity and rapid evolution, may play a key role in driving viral diversity.
Manipulation of the microRNA172 -AP2L2interaction provides precise control of wheat and triticale plant height
Authors: Zhang Chaozhong , Hegarty Joshua , Padilla Mariana , Tricoli David M. , Dubcovsky Jorge , Debernardi Juan M.
Published: August 2024

TheREDUCED HEIGHT(RHT) dwarfing allelesRht-B1bandRht-D1bwere essential in the “Green Revolution” to optimize wheat plant height and increase grain yield. However, those alleles reduce coleoptile length limiting sowing depth, which triggered the search for alternative dwarfing genes. In this study, we engineered the interaction between miR172 andAP2L2genes to fine-tune wheat and triticale plant height without affecting coleoptile and first-leaf length.
Novel Perceval Sizing Technique: Single Center Experience
Authors: Margaryan Rafik , Concistre Giovanni , Bianchi Giacomo , Solinas Marco
Published: August 2024

Objective

Aim of this study was to compare old (manufacturer recommended) and new (institution based) sizing techniques for sutureless valve.

Materials

A 226 consecutively operated patients underwent aortic valve replacement with Perceval sutureless valve (Corcym) and had CT scan with contrast enhancement were included to this study. The final decision of appropriate size is based on intra-operative obturator sizing. Briefly, we have measured on the CT scans the annular ring surface and perimeter in order to estimate the prosthesis size. New sizing technique uses only white obturator of Perceval and it should passe trough the annulus with slight friction, which practically under-sizes with respect to manufacturer’s recommendations.

Results

The operative mortality was 1 (0.4424779%). There were no prosthesis migration neither annular rupture in any group. The mean follow up was lower in new group (3.3 ± 2.0 vs 9.7 ± 1.6, p < 0.01). At the discharge the patients who have used the new sizing technique had less gradient on the prosthetic valve (13.4 ± 5.0 vs 15.2 ± 5.5, p = 0.02). The new sizing was less prone to degeneration at the follow-up which would require intervention (13.4 ± 5.0 vs 15.2 ± 5.5, p = 0.02). Oversizing of 22.6% had significant role on valve gradient increase and structural degeneration (p< 0.05).

Conclusions

New sizing technique is safe and reproducible. It seem to deliver better immediate and long term benefits for Perceval sutureless valve, less postoperative gradient, less probability or structural degeneration.
Decoding critical targets and signaling pathways in EBV-mediated diseases using large language models
Authors: Yu Jingwen , Wang Yaohao , Wang Haidong , Wei Zhi , Pei Yonggang
Published: August 2024

Epstein-Barr virus (EBV), a member of the gamma-herpesvirus, is the first identified human oncovirus and is associated with various malignancies. Understanding the intricate interactions between EBV antigens and cellular pathways is crucial to unravel the molecular mechanisms in EBV-mediated diseases. However, fully elucidating EBV-host interactions and the associated pathogenesis remains a significant challenge. In this study, we utilized LLMs to screen 36,105 EBV-relevant scientific publications, presenting a descriptive overview of the interactions between EBV antigens and host cellular pathways through comprehensive interaction networks. We described the critical roles of EBV antigens by constructing functional subsets of host proteins targeted by EBV antigens and illustrated the interactions using protein- protein interaction (PPI) networks. Furthermore, we developed an antigen-pathway network that highlights the connections with EBV-associated diseases, including DLBCL, BL, NPC, gastric cancer (GC), and post-transplant lymphoproliferative disorders (PTLD). Utilizing our dataset and public dataset, we validated the efficacy of using BLLF3-targeted TLR2-associated factors as marker genes for DLBCL. Next, we confirmed the co-expression of calcium pathway factors induced by LMP1 over- expression in BL. Finally, based on shared results suggesting that LMP1 actively regulates the glycolysis pathway, we identified and validated the correlation and co- expression of LMP1-induced PARP1, HIF1A, HOXB3, and key transcription-related factors, revealing the complete picture of LMP1’s influence on the glycolysis pathway. Our study presents a comprehensive functional encyclopedia of the interactions between EBV antigens and host signaling pathways across various EBV-associated disease contexts, providing valuable insights for the development of therapeutic strategies.
Quantifying the Impact of Co-Housing on Murine Aging Studies
Authors: Luciano Alison , Churchill Gary A.
Published: August 2024

Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are indepen-dent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20 thousand observations. We show that the independence assumption underlying common analytic techniques does not hold in these data, particularly for traits associated with frailty. We describe and demonstrate various analytical tools available to accommodate this study design and highlight a limitation of standard variance components models (i.e., linear mixed models) which are the usual statisti-cal tool for handling correlated errors. Through simulations, we examine the statistical biases resulting from intra-cage correlations with similar magnitudes as observed in these case studies and discuss implications for power and reproducibility.
Challenges and lessons learned from preliminary modeling of with-in herd transmission of highly pathogenic avian influenza H5N1in dairy cattle
Authors: Bellotti Brinkley Raynor , DeWitt Michael E. , Wenner Jennifer J. , Lombard Jason E. , McCluskey Brian J. , Kortessis Nicholas
Published: August 2024

The emergence of highly pathogenic avian influenza A H5N1in dairy cattle raises many questions related to animal health and changes to the risk of an epidemic in humans. We synthesized information currently published to fit a compartment model of H5N1transmission within a dairy herd. An accompanying web application allows users to run simulations for specific outbreak scenarios. We estimatedR0near 1.2 with a short duration of infectiousness and fast time course of an epidemic within a farm, which we discuss in the context of possible on-farm control strategies. The web application allows users to simulate consequences of an epidemic using herd-specific information, a tool we propose will help inform stakeholders about potential consequences of uncontrolled H5N1spread. Our modeling work has identified several key information gaps that would strengthen our understanding and control of this emerging infectious disease.
Resource-use plasticity governs the causal relationship between traits and community structure in model microbial communities
Authors: McGuinness Brendon , Weber Stephanie C. , Guichard Frédéric
Published: August 2024

Resolving the relationship between species’ traits and their relative abundance is a central challenge in ecology. Current hypotheses assume relative abundances either result from or are independent of traits. However, despite some success, these hypotheses do not integrate the reciprocal and feedback interactions between traits and abundances to predictions of community structure such as relative abundance distributions. Here we study how plasticity in resource-use traits govern the causal relationship between traits and relative abundances. We adopt a consumer-resource model that incorporates resource-use plasticity that operates to optimize organism growth, underpinned by investment constraints in physiological machinery for acquisition of resources. We demonstrate that the rate of plasticity controls the coupling strength between trait and abundance dynamics, predicting species’ relative abundance variation. We first show how plasticity in a single species in a community allows all other non-plastic species to coexist, a case of facilitation emerging from competitive interactions where a plastic species minimizes its similarity with competitors and maximizes resource-use efficiency in its environment. We apply this environment-competition trade-off to predict trait-abundance relationships and reveal that initial traits are better predictors of equilibrium abundances than final trait values. This result highlights the importance of transient dynamics that drive species sorting. The temporal scale of transients determines the strength of species sorting due to the emergence of ‘ecological equivalence’ at equilibrium. We propose trait-abundance feedback as an eco-evolutionary mechanism linking community structure and assembly, highlighting trait plasticity’s role in community dynamics.
Predicting mutation-disease associations through protein interactions via deep learning
Authors: Li Xue , Cao Ben , Wang Jianmin , Meng Xiangyu , Wang Shuang , Huang Yu , Petretto Enrico , Song Tao
Published: August 2024

Disease is one of the primary factors affecting life activities, with complex etiologies often influenced by gene expression and mutation. Currently, wet-lab experiments have analyzed the mechanisms of mutations, but these are usually limited by the costs of wet experiments and constraints in sample types and scales. Therefore, this paper constructs a real-world mutation-induced disease dataset and proposes Capsule networks and Graph topology networks with multi-head attention (CGM) to predict the mutation-disease associations. CGM can accurately predict protein mutation-disease associations, and in order to further elucidate the pathogenicity of protein mutations, we also verified that protein mutations lead to protein structural alterations by Swiss-model, which suggests that mutation-induced conformational changes may be an important pathogenic factor. Limited by the size of the mutated protein dataset, we also performed experiments on benchmark and imbalanced datasets, where CGM mined 22 unknown protein interaction pairs from the benchmark dataset, better illustrating the potential of CGM in predicting mutation-disease associations. In summary, this paper curates a real dataset and proposes CGM to predict the protein mutations-disease associations, providing a novel tool for further understanding of biomolecular pathways and disease mechanisms.
Synaptic cell adhesion moleculeCdh6identifies a class of sensory neurons with novel functions in colonic motility
Authors: Gomez-Frittelli Julieta , Devienne Gabrielle , Travis Lee , Kyloh Melinda A. , Duan Xin , Hibberd Tim J. , Spencer Nick J. , Huguenard John R. , Kaltschmidt Julia A.
Published: August 2024

Intrinsic sensory neurons are an essential part of the enteric nervous system (ENS) and play a crucial role in gastrointestinal tract motility and digestion. Neuronal subtypes in the ENS have been distinguished by their electrophysiological properties, morphology, and expression of characteristic markers, notably neurotransmitters and neuropeptides. Here we investigated synaptic cell adhesion molecules as novel cell type markers in the ENS. Our work identifies two Type II classic cadherins,Cdh6andCdh8,specific to sensory neurons in the mouse colon. We show thatCdh6+neurons demonstrate all other distinguishing classifications of enteric sensory neurons including marker expression ofCalcbandNmu, Dogiel type II morphology and AH-type electrophysiology andIHcurrent. Optogenetic activation ofCdh6+sensory neurons in distal colon evokes retrograde colonic motor complexes (CMCs), while pharmacologic blockade of rhythmicity-associated currentIHdisrupts the spontaneous generation of CMCs. These findings provide the first demonstration of selective activation of a single neurochemical and functional class of enteric neurons, and demonstrate a functional and critical role for sensory neurons in the generation of CMCs.

One-Sentence Summary

Intrinsic sensory neurons of the enteric nervous system in the mouse distal colon exclusively express synaptic cell adhesion moleculesCdh6andCdh8,evoke retrograde colonic motor complexes (CMCs) when stimulated, and possess rhythmicity-associatedIHcurrent, involved in producing spontaneous CMCs.
RiboSnake – a user-friendly, robust, reproducible, multipurpose and documentation-extensive pipeline for 16S rRNA gene microbiome analysis
Authors: Dörr Ann-Kathrin , Welling Josefa , Dörr Adrian , Gosch Jule , Möhlen Hannah , Schmithausen Ricarda , Kehrmann Jan , Meyer Folker , Kraiselburd Ivana
Published: August 2024

Background

Next-generation sequencing for assaying microbial communities has become a standard technique in recent years. However, the initial investment required into in-silico analytics is still quite significant, especially for facilities not focused on bioinformatics. With the rapid decline in costs and growing adoption of sequencing-based methods in a number of fields, validated, fully automated, reproducible and yet flexible pipelines will play a greater role in various scientific fields in the future.

Results

We present RiboSnake, a validated, automated, reproducible QIIME2-based analysis pipeline implemented in Snakemake for the computational analysis of16S rRNAgene amplicon sequencing data. The pipeline comes with pre-packaged validated parameter sets, optimized for different sample types. The sets range from complex environmental samples to patient data. The configuration packages can be easily adapted and shared, requiring minimal user input.

Conclusion

RiboSnake is a new alternative for researchers employing16S rRNAgene amplicon sequencing and looking for a customizable and yet user-friendly pipeline for microbiome analysis with in-vitro validated settings. The complete analysis generated with a fully automated pipeline based on validated parameter sets for different sample types is a significant improvement to existing methods. The workflow repository can be found on GitHub (https://github.com/IKIM-Essen/RiboSnake).
Processivity of the monomeric KLP-6 kinesin and a Brownian ratchet model with symmetric potentials
Authors: Kita Tomoki , Sasaki Kazuo , Niwa Shinsuke
Published: August 2024

Most kinesin molecular motors dimerize to move processively and efficiently along microtubules; however, some can maintain processivity even in a monomeric state. Previous studies have suggested that asymmetric potentials between the motor domain and microtubules underlie this motility. In this study, we demonstrate that the kinesin-3 family motor protein KLP-6 can move along microtubules as a monomer upon release of autoinhibition. This motility can be explained by a change in length between the head and tail, rather than by asymmetric potentials. Using mass photometry and single-molecule assays, we confirmed that activated full-length KLP-6 is monomeric both in solution and on microtubules. KLP-6 possesses a microtubule-binding tail domain, and its motor domain does not exhibit biased movement, indicating that the tail domain is crucial for the processive movement of monomeric KLP-6. We developed a mathematical model to explain the unidirectional movement of monomeric KLP-6. Our model concludes that a slight conformational change driven by neck-linker docking in the motor domain enables the monomeric kinesin to move unidirectionally if a second microtubule-binding domain exists.

SIGNIFICANCE

Kinesin molecular motors are designed to move efficiently using two heads. Studying these biological molecular motors provides valuable insights into the mechanisms that generate unidirectional movements amidst intense thermal fluctuations. This study reveals that the monomeric kinesin-3 KLP-6 can move along microtubules through interactions with its tail domain. The proposed Brownian ratchet model explains this movement by considering a change in stalk length caused by neck-linker docking rather than asymmetric potentials. This model suggests that a slight conformational change can achieve robust processive movement of kinesin. These findings have significant implications for understanding Brownian ratchet motors and designing rational artificial molecular motors.
Identifying crosstalks among post-translational modifications in lung cancer proteomic data
Authors: Lai Shengzhi , DAI Shuaijian , Zhao Peize , Zhou Chen , Li Ning , Yu Weichuan
Published: August 2024

In a lung squamous cell carcinoma data set containing over 20 million tandem mass spectra, we identified 860 peptides with post-translational modifications (PTMs) that were significantly upregulated in lung cancer samples as compared to normal samples using our new search engine named PIPI3. Among the modified peptides related to upregulated gene ontology terms, about 50% carried multiple PTMs. PIPI3 demonstrated its enabling power to provide insight into PTM crosstalk research.