bluuebunny/crossref_metadata_2025 huggingface dataset:
A Geometrical Explanation for Change in Pelvic Tilt (or Lack of Change) Following Long Spinal Fusions
Authors: Prabhakar Gautham , Kelly Michael P. , Koslosky Ezekial , Eck Andrew , Emukah Chimobi , Chaput Christopher , Hills Jeffrey
Published: February 2024

Study Design.

Retrospective cohort.

Objective.

Examine the relationship between compensatory pelvic retroversion, positive sagittal imbalance (measured by C2 tilt), and the C2 pelvic angle (C2PA) in patients before long spinal fusions; and to determine the association between changes in C2PA and pelvic tilt (PT) following long spinal fusions.

Background.

Adult spinal deformity surgical goals often include a PT target, yet patients frequently demonstrate persistent compensatory pelvic retroversion following surgery.

Methods.

Adults above 18 years old undergoing long spinal fusions (>4 levels) with standing preoperative and postoperative radiographs were included. To examine drivers of preoperative sagittal balance, regression models were fit to estimate the association between preoperative C2PA and pelvic incidence with preoperative PT and C2 tilt. To predict postoperative change in PT, multivariable regression was used to estimate change in PT, adjusting for change in C2PA and preoperative C2 tilt.

Results.

Among the 80 patients identified, the median age was 61 (IQR: 45–72) and 46 (58%) were female. The median number of levels fused was 10 (IQR: 8–13) and 55 (69%) were instrumented to the sacrum/pelvis. Preoperative C2PA had a significant nonlinear association with preoperative PT (r2=0.81,P<0.001) and preoperative C2 tilt (r2=0.41,P=0.002). Postoperative change in PT was strongly associated with change in C2PA (β=0.81;P<0.001) and preoperative C2 tilt (β=0.55;P<0.001).

Conclusions.

Following long spinal fusions, change in PT (or lack thereof) can be reliably predicted based on change in C2PA and preoperative C2 tilt. In patients with normal preoperative C2 tilt, the change in C2PA is nearly equivalent to the change in PT, but in patients with more positive C2 tilt (sagittal imbalance), a greater change in C2PA will be required to achieve an equivalent change in PT.

Level of Evidence.

3.
Thumb Carpometacarpal Hemi-trapeziectomy: Creating a Balanced Arthroplasty
Authors: Razavi S. Amir , Pakvasa Mikhail , Sullivan Connor , Rafijah Gregory H.
Published: February 2024

Background:

Thumb carpometacarpal (CMC) joint arthritis is commonly encountered in Hand Surgery practice and can be quite disabling. Surgery is the best option for patients who have failed conservative management for thumb CMC arthritis. There are numerous surgical options to address thumb CMC arthritis with no clear advantage of one technique over the other.

Methods:

In this paper, we present our patient selection criteria and technique of hemi-trapeziectomy with interpositional arthroplasty for patients with thumb CMC arthritis.

Conclusions:

Hemi-trapeziectomy is ideal for patients with Eaton stage II/III thumb CMC arthritis in whom the STT joint is spared.
Simulating the Simultaneous Impact of Medication for Opioid Use Disorder and Naloxone on Opioid Overdose Death in Eight New York Counties
Authors: Cerdá Magdalena , Hamilton Ava D. , Hyder Ayaz , Rutherford Caroline , Bobashev Georgiy , Epstein Joshua M. , Hatna Erez , Krawczyk Noa , El-Bassel Nabila , Feaster Daniel J. , Keyes Katherine M.
Published: February 2024

Background:

The United States is in the midst of an opioid overdose epidemic; 28.3 per 100,000 people died of opioid overdose in 2020. Simulation models can help understand and address this complex, dynamic, and nonlinear social phenomenon. Using the HEALing Communities Study, aimed at reducing opioid overdoses, and an agent-based model, Simulation of Community-Level Overdose Prevention Strategy, we simulated increases in buprenorphine initiation and retention and naloxone distribution aimed at reducing overdose deaths by 40% in New York Counties.

Methods:

Our simulations covered 2020–2022. The eight counties contrasted urban or rural and high and low baseline rates of opioid use disorder treatment. The model calibrated agent characteristics for opioid use and use disorder, treatments and treatment access, and fatal and nonfatal overdose. Modeled interventions included increased buprenorphine initiation and retention, and naloxone distribution. We predicted a decrease in the rate of fatal opioid overdose 1 year after intervention, given various modeled intervention scenarios.

Results:

Counties required unique combinations of modeled interventions to achieve a 40% reduction in overdose deaths. Assuming a 200% increase in naloxone from current levels, high baseline treatment counties achieved a 40% reduction in overdose deaths with a simultaneous 150% increase in buprenorphine initiation. In comparison, low baseline treatment counties required 250–300% increases in buprenorphine initiation coupled with 200–1000% increases in naloxone, depending on the county.

Conclusions:

Results demonstrate the need for tailored county-level interventions to increase service utilization and reduce overdose deaths, as the modeled impact of interventions depended on the county’s experience with past and current interventions.
Gastric myeloid sarcoma mimicking pseudoachalasia in non-leukemic context - a singular case report
Authors: Jebrini Nidal , Sarahneh Husein , Jaber Mohanad , Natsheh Motaz , Abu Ayyash Ahmad , Bannoura Sami , Razem Raghad
Published: February 2024

Introduction and Importance:

Myeloid sarcoma (MS) is a rare tumor associated with acute myeloid leukemia (AML) and occasionally occurs independently. It typically affects skin, bone, lymph nodes, and rarely the gastrointestinal tract, with gastric cases being extremely rare. Notably, no reported instances associate pseudoachalasia with gastric myeloid sarcoma.

Case Presentation:

A 20-year-old male presented with severe dysphagia, refractory vomiting, and weight loss. Diagnosed with type III achalasia via esophageal tests, subsequent gastroscopy revealed a large gastric mass, later identified as gastric myeloid sarcoma through histopathology.

Clinical Discussion:

MS, characterized by immature blast cells, poses diagnostic challenges without typical leukemia symptoms. Diagnosis involves immunohistochemistry, employing markers like CD33, CD34, and CD43. Optimal treatments, such as chemotherapy or stem cell transplantation, aim to delay leukemia progression. Gastric primary de novo myeloid sarcoma is exceedingly rare, emphasizing the need for tailored treatment strategies.

Conclusion:

Gastric myeloid sarcoma is an exceptionally rare tumor, especially without concurrent acute myeloid leukemia (AML), complicating its diagnosis. This case represents the first globally documented instance of gastric myeloid sarcoma causing pseudo-achalasia. Documenting this unique clinical presentation is crucial for a better grasp of gastric myeloid sarcoma’s diverse manifestations.
Prospective Cohort Study of Treatment Outcomes of Vaginal Discharge Syndrome in Women in Windhoek, Namibia
Authors: Dunaiski Cara M. , Kock Marleen M. , Jung Hyunsul , Peters Remco P.H.
Published: February 2024

Background

Syndromic treatment is the standard of care for vaginal discharge syndrome (VDS) in resource-constrained settings. However, the outcomes of VDS treatment have not been well documented. This study aimed to determine the incidence, risk factors, and microbial etiology of treatment failure in women with VDS.

Methods

This prospective cohort study of women with VDS was conducted between September 2021 and March 2022 at Katutura Intermediate Hospital in Windhoek, Namibia. Microbiological analyses of sexually transmitted infections (STIs;Chlamydia trachomatis,Neisseria gonorrhoeae,Trichomonas vaginalis,Mycoplasma genitalium), bacterial vaginosis, and vulvovaginal candidiasis (VVC) were performed. Treatment outcomes were assessed at 7 and 30 days after treatment, followed by microbial investigation in case of treatment failure.

Results

One hundred nine women were enrolled, and 94 (86%) completed the follow-up. At baseline, 58 of 109 women (53%) were diagnosed with STI, 47 of 109 (43%) with bacterial vaginosis, and 45 of 109 (41%) with VVC.Candida albicans(33 of 45; 73%) was the main pathogen in VVC, with fluconazole resistance detected in 8 of 33 isolates (24%); 10 of 12 (80%) of non–albicans Candidaspecies showed resistance. The incidence of treatment failure was 3.6 per 100 person-years at 7 days and 1.0 per 100 person-years at 30 days of follow-up; 17 of 94 women (18%) had recurrent VDS, and 12 of 94 women (13%) had persistent VDS. Vulvovaginal candidiasis (odds ratio, 4.3; 95% confidence interval, 1.7–11;P= 0.002) at baseline was associated with treatment failure.

Conclusions

Treatment failure after syndromic management of VDS is common in resource-constrained settings. Access to diagnostic testing, including fungal culture and susceptibility testing, is recommended to improve outcomes.
A Retrospective Cohort Study of At-Home Catheter Removal After Urogynecologic Surgery
Authors: Davenport Abigail P. , Li Yi W. , Lefbom Lucie T. , Iglesia Cheryl B. , Dieter Alexis A.
Published: February 2024

Importance

In-office postoperative voiding trials (VTs) increase health care burden for patients and physicians. Adoption of an at-home VT option may decrease burden without increasing adverse events postoperatively.

Objective

The purpose of this study was to compare 30-day postoperative outcomes between participants who performed an at-home autofill VT after catheter self-discontinuation during the Assessing Healthcare Utilization and Feasibility of Transurethral Catheter Self-discontinuation (FLOTUS) study and a “historic” control cohort of patients who presented to the office for backfill-assisted VT on postoperative day (POD) 1.

Study Design

This was a retrospective cohort study of women with postoperative urinary retention after urogynecologic surgery between June 2020 and March 2022. Outcomes from the FLOTUS study were compared with a “historic” control cohort of patients that were identified on chart review from the year before FLOTUS initiation. Demographic, medical history, and procedure-related data were collected. Thirty-day outcome data included office calls/messages, office visits, emergency department visits, complications, and catheterization outcomes.

Results

Forty-six participants were included in the FLOTUS cohort and 65 participants in the historic cohort. There was no difference in the POD1 VT pass rate, number of office calls/messages, emergency department visits, or postoperative complications between the 2 cohorts. The FLOTUS patients attended 1 less office visit (1 vs 2 office visits, P<0.001), and this difference persisted on regression analysis (−0.87 office visits; 95% CI, −1.18 to −0.56, P<0.001).

Conclusion

Patients who had backfill-assisted VTs on POD1 attended 1 additional office visit compared with those who removed their catheters at home.
Lessons From the Coronavirus Disease Experience
Authors: Sewell Margaret , Neugroschl Judith , Zhu Carolyn W. , Loizos Maria , Zeng Xiaoyi , Pun Kelly , Greenberg Jonathan , Velasco Nelly , Sheppard Faye , Tocco Carly , Evans Kirsten , Ardolino Allison , Meuser Caroline , Li Clara , Melnick Jonah , Grossman Hillel , Sano Mary
Published: February 2024

Objective:

In New York City in 2020 the pandemic shut down in-person research. Icahn School of Medicine’s Alzheimer’s Disease Research Center transitioned longitudinal evaluations from in-person to telephone to enhance equity of access. We assessed diverse research participants’ and clinical research coordinators’ (CRC) satisfaction with remote evaluation and examined sociodemographic, cognitive, and behavioral factors that might impact satisfaction.

Methods:

Data collected: 241 participants with Clinical Dementia Rating (CDR) = 0/0.5 (3/2020 to 6/2021). A Telehealth Satisfaction Questionnaire for CRCs and participants was administered at the end of remote evaluations. We compared Telehealth Satisfaction Questionnaire items by CDR and Geriatric Depression Scale.

Results:

Participants’ mean age was 78.4, 61.4% were females, 16.2% were Hispanic, 17.1% Asian, 15.8% were non-Hispanic black, and 72.6% CDR = 0. Participant satisfaction was high [14.1 ± 1.4 (out of 15)] but was lower among those with depression. CRC satisfaction was high [16.9 ± 1.8 (out of 18)] but was lower concerning the ability to explain the test battery and interact with participants with CDR = 0.5.

Conclusion:

Telephone research assessments provide flexibility in a hybrid model. They offer equitable access to research participation for those who do not use computer technology and may promote the retention of diverse elderly research participants.
Remission of Obesity-Related Sleep Apnea and Its Effect on Mortality and Cardiovascular Events after Metabolic and Bariatric Surgery: A Propensity-Matched Cohort Study
Authors: Stenberg Erik , Ottosson Johan , Näslund Erik
Published: February 2024

BACKGROUND:

Although obstructive sleep apnea (OSA) is common among patients with obesity and linked to cardiovascular disease, there is a lack of studies evaluating the effects of reaching remission from OSA after metabolic and bariatric surgery.

STUDY DESIGN:

A registry-based nationwide study including patients operated with sleeve gastrectomy or Roux-en-Y gastric bypass from 2007 until 2019 in Sweden. Patients who reached remission of OSA were compared with those who did not reach remission and a propensity score-matched control group of patients without OSA at the time of operation. The main outcome was overall mortality, and secondary outcome was major cardiovascular events (MACEs).

RESULTS:

In total, 5,892 patients with OSA and 11,552 matched patients without OSA completed a 1-year follow-up and were followed for a median of 6.8 years. Remission of OSA was seen for 4,334 patients (74%). Patients in remission had a lower risk for overall mortality (cumulative incidence 6.0% vs 9.1%; p < 0.001) and MACE (cumulative incidence 3.4% vs 5.8%; p < 0.001) at 10 years after operation compared with those who did not reach remission. The risk was similar to that of the control group without OSA at baseline (cumulative incidence for mortality 6%, p = 0.493, for MACE 3.7%, p = 0.251).

CONCLUSIONS:

The remission rate of OSA was high after metabolic and bariatric surgery. This was in turn associated with reduced risk for death and MACE compared with patients who did not achieve remission reaching a similar risk seen among patients without OSA at baseline. A diligent follow-up of patients who do not reach remission remains important.
Cell type-specific functions of Alzheimer's disease endocytic risk genes
Authors: Maninger Johanna-Katharina , Nowak Karolina , Goberdhan Srilakshmi , O'Donoghue Rachel , Connor-Robson Natalie
Published: February 2024

Endocytosis is a key cellular pathway required for the internalization of cellular nutrients, lipids and receptor-bound cargoes. It is also critical for the recycling of cellular components, cellular trafficking and membrane dynamics. The endocytic pathway has been consistently implicated in Alzheimer's disease (AD) through repeated genome-wide association studies and the existence of rare coding mutations in endocytic genes.
BIN1
and
PICALM
are two of the most significant late-onset AD risk genes after
APOE
and are both key to clathrin-mediated endocytic biology. Pathological studies also demonstrate that endocytic dysfunction is an early characteristic of late-onset AD, being seen in the prodromal phase of the disease. Different cell types of the brain have specific requirements of the endocytic pathway. Neurons require efficient recycling of synaptic vesicles and microglia use the specialized form of endocytosis—phagocytosis—for their normal function. Therefore, disease-associated changes in endocytic genes will have varied impacts across different cell types, which remains to be fully explored. Given the genetic and pathological evidence for endocytic dysfunction in AD, understanding how such changes and the related cell type-specific vulnerabilities impact normal cellular function and contribute to disease is vital and could present novel therapeutic opportunities.

This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.
VPS35 and retromer dysfunction in Parkinson's disease
Authors: Rowlands Jordan , Moore Darren J.
Published: February 2024

The
vacuolar protein sorting 35 ortholog
(
VPS35
) gene encodes a core component of the retromer complex essential for the endosomal sorting and recycling of transmembrane cargo. Endo-lysosomal pathway deficits are suggested to play a role in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Mutations in
VPS35
cause a late-onset, autosomal dominant form of PD, with a single missense mutation (D620N) shown to segregate with disease in PD families. Understanding how the PD-linked D620N mutation causes retromer dysfunction will provide valuable insight into the pathophysiology of PD and may advance the identification of therapeutics. D620N VPS35 can induce LRRK2 hyperactivation and impair endosomal recruitment of the WASH complex but is also linked to mitochondrial and autophagy-lysosomal pathway dysfunction and altered neurotransmitter receptor transport. The clinical similarities between
VPS35
-linked PD and sporadic PD suggest that defects observed in cellular and animal models with the
D620N VPS35
mutation may provide valuable insights into sporadic disease. In this review, we highlight the current knowledge surrounding VPS35 and its role in retromer dysfunction in PD. We provide a critical discussion of the mechanisms implicated in
VPS35
-mediated neurodegeneration in PD, as well as the interplay between VPS35 and other PD-linked gene products.

This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.
Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers
Authors: Herman Mathieu , Randall Grace W. , Spiegel Julia L. , Maldonado Delphina J. , Simoes Sabrina
Published: February 2024

Over the past two decades, increased research has highlighted the connection between endosomal trafficking defects and neurodegeneration. The endo-lysosomal network is an important, complex cellular system specialized in the transport of proteins, lipids, and other metabolites, essential for cell homeostasis. Disruption of this pathway is linked to a wide range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and frontotemporal dementia. Furthermore, there is strong evidence that defects in this pathway create opportunities for diagnostic and therapeutic intervention. In this
Opinion
piece, we concisely address the role of endo-lysosomal dysfunction in five neurodegenerative diseases and discuss how future research can investigate this intracellular pathway, including extracellular vesicles with a specific focus on exosomes for the identification of novel disease biomarkers.

This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.
Endo-lysosomal dysfunction and neuronal–glial crosstalk in Niemann–Pick type C disease
Authors: Malara Mariagiovanna , Prestel Matthias , Tahirovic Sabina
Published: February 2024

Niemann–Pick type C (NPC) disease is a rare progressive lysosomal lipid storage disorder that manifests with a heterogeneous spectrum of clinical syndromes, including visceral, neurological and psychiatric symptoms. This monogenetic autosomal recessive disease is largely caused by mutations in the
NPC1
gene, which controls intracellular lipid homeostasis. Vesicle-mediated endo-lysosomal lipid trafficking and non-vesicular lipid exchange via inter-organelle membrane contact sites are both regulated by the NPC1 protein. Loss of NPC1 function therefore triggers intracellular accumulation of diverse lipid species, including cholesterol, glycosphingolipids, sphingomyelin and sphingosine. The NPC1-mediated dysfunction of lipid transport has severe consequences for all brain cells, leading to neurodegeneration. Besides the cell-autonomous contribution of neuronal NPC1, aberrant NPC1 signalling in other brain cells is critical for the pathology. We discuss here the importance of endo-lysosomal dysfunction and a tight crosstalk between neurons, oligodendrocytes, astrocytes and microglia in NPC pathology. We strongly believe that a cell-specific rescue may not be sufficient to counteract the severity of the NPC pathology, but targeting common mechanisms, such as endo-lysosomal and lipid trafficking dysfunction, may ameliorate NPC pathology.

This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.
General Capillary Endothelial Cells Undergo Reprogramming into Arterial Endothelial Cells in Pulmonary Hypertension through HIF-2α/Notch4 Pathway
Authors: Liu Bin , Yi Dan , Xia Xiaomei , Ramirez Karina , Zhao Hanqiu , Cao Yanhong , Tripathi Ankit , Dong Ryan , Gao Anton , Ding Hongxu , Qiu Shenfeng , Kalinichenko Vladimir V. , Fallon Michael B. , Dai Zhiyu
Published: February 2024

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of distal capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear. Our recent single-cell RNA sequencing, spatial transcriptomics analysis, RNASCOPE, and immunostaining analysis showed that arterial ECs accumulation and loss of capillary ECs were evident in human PAH patients and pulmonary hypertension (PH) rodents. Pseudotime trajectory analysis of the single-cell RNA sequencing data suggest that lung capillary ECs transit to arterial ECs during the development of PH. Our study also identified CXCL12 as the marker for arterial ECs in PH. Capillary EC lineage tracing approach using capillary specific-Dre;Tdtomato reporter mice demonstrated that capillary ECs gave rise to arterial ECs during PH development. Genetic deletion of HIF-2a or pharmacological inhibition of Notch4 normalized the arterial programming in PH. In conclusion, our study demonstrates that capillary endothelium transits to arterial endothelium through the HIF-2a-Notch4 pathway during the development of PAH. Thus, targeting arterial EC transition might be a novel approach for treating PAH patients.
High-frequency amplitude-modulated sinusoidal stimulation induces desynchronized yet controllable neural firing
Authors: Barra Beatrice , Kumar Ritesh , Gopinath Chaitanya , Mirzakhalili Ehsan , Lempka Scott F. , Gaunt Robert A. , Fisher Lee E.
Published: February 2024

Regaining sensory feedback is pivotal for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore focal percepts in the missing limb. However, conventional rectangular current pulses induce sensations often described as unnatural. This is likely due to the synchronous and periodic nature of activity evoked by these pulses. Here we introduce a fast-oscillating amplitude-modulated sinusoidal (FAMS) stimulation waveform that desynchronizes evoked neural activity. We used a computational model to show that sinusoidal waveforms evoke asynchronous and irregular firing and that firing patterns are frequency dependent. We designed the FAMS waveform to leverage both low- and high-frequency effects and found that membrane non-linearities enhance neuron-specific differences when exposed to FAMS. We implemented this waveform in a feline model of peripheral nerve stimulation and demonstrated that FAMS-evoked activity is more asynchronous than activity evoked by rectangular pulses, while being easily controllable with simple stimulation parameters. These results represent an important step towards biomimetic stimulation strategies useful for clinical applications to restore sensory feedback.
Effect of Light and Water Agitation on Hatching Processes in Clown Anemonefish Amphiprion ocellaris
Authors: Yamanaka Sakuto , Kawaguchi Mari , Yasumasu Shigeki , Sato Kenji , Kinoshita Masato
Published: February 2024

Clown anemonefish (Amphiprion ocellaris) exhibit an environmentally cued hatching strategy, wherein parents generate water flow to encourage embryos to hatch after sunset on the eighth day post spawning. Although previous studies have shown that hatching requires complete darkness and water agitation, the regulatory mechanisms underlying these environmental cues remain elusive. This study investigated the expression patterns of hatching enzymes and how darkness and water agitation affect their secretion and the digestion of the egg envelope (chorion) in clown anemonefish. We revealed that hatching enzymes were expressed from the early developmental stages and decreased towards hatching day, similar to other fish species. The hatching gland cells were located on the tail, which may be associated with egg shape and chorion breakage. On the day of hatching, chorion digestion occurred exclusively in complete darkness, regardless of water agitation. In addition, ionomycin, a Ca2+ ionophore and an inducer of hatching enzyme secretion, triggered chorion digestion even under light-on conditions. Furthermore, water agitation expedited chorion digestion in the dark. In conclusion, our findings indicate that darkness triggers the secretion of hatching enzymes mediated by changes in Ca2+ levels, whereas water agitation assists chorion digestion activity and/or hatching enzyme secretion. These responses to environmental cues contribute to the rapid and synchronised hatching in clown anemonefish.
Molecular characterization and culture optimization of marine copepod Oithona dissimilis (Landberg, 1940) from Nagore coastal waters, Southern India
Authors: PILIYAN Raju P , Perumal Santhanam , Barathan Balaji Prasath , Meril Divya , Ragothaman Prathiviraj , Shanmugam Gunabal , Pachippan Perumal
Published: February 2024

This study focused on identifying the cyclopoid copepod Oithona dissimilis found in the Nagore coastal waters of Southern India. Based on both morphological and molecular approaches to identify this species. Morphological characters were confirmed by examining the arrangement of setae and spines on the exopod of swimming legs 1-4. Molecular studies were performed using the CO 1 gene, which proved an effective marker for species identification. After identifying the Oithona dissimilis, reared them under laboratory conditions to determine the effects of various environmental parameters on their survival, nauplii production, and population density. Tested different temperatures, light intensity, pH, salinity, and diets and found that the optimum conditions for rearing Oithona dissimilis under laboratory conditions were a salinity of 25 PSU, a temperature range of 24-28 C, pH of 8, light intensity of 500 lux, and a mixed algal diet at a concentration of 30,000 cells/ml. The present study confirms the importance of accurate taxonomic identification for the Oithona group at the species level. Additionally, our findings show that rearing cyclopoid copepods under laboratory conditions that mimic their natural range of environmental parameters is crucial for the thriving culture of these organisms, the aquaculture industry frequently utilizes this as a live feed.
Scale Cortisol Modulation in Cultured Nile Tilapia (Oreochromis niloticus): Deciphering the Intricate Role in Chronic Stress through Mitogen-Activated Protein Kinase Signaling Pathway Regulation
Authors: Mwaura John Gitau , Angienda Paul Oyieng , Wekesa Clabe , Namuyenga Eunice Toko , Ogutu Philip , Okoth Patrick
Published: February 2024

Chronic stress poses a significant challenge to aquaculture production, and cortisol and glucose have traditionally served as stress markers. However, recent doubts have emerged about the reliability of scale cortisol as a chronic stress determinant due to its involvement in calcium homeostasis. While cortisol influences gene expression in the stress response cascade, few studies explore its impact on metabolic pathways in cultured Nile tilapia. This study delves into the relationship between cortisol signatures of chronic stress in Nile tilapia and the regulation of the Mitogen Activated Protein Kinase (MAPK) signalling pathway, crucial for cell processes. Juvenile Nile tilapia were subjected to different ammonia concentrations and stocking densities for 70 days, with assessments of growth performance, stress levels, RNA sequencing, and differential gene expression. The results revealed a positive correlation between stressors and blood glucose, plasma cortisol, and scale cortisol concentrations. Fish in water with 0.8 mg/L ammonia exhibited elevated plasma glucose and cortisol, while those in 1.2 mg/L showed increased scale cortisol. Higher stocking densities also correlated with elevated stress markers. Notably, cortisol levels rose with ammonia concentration and stocking density, negatively impacting growth performance. The MAPK signalling pathway, linked to cell processes, showed significant downregulation with increasing ammonia concentrations, suggesting its sensitivity to stress. Taken together, six genes in this pathway were significantly enriched following ammonia treatment (Padj less than or equal to 0.05) i.e. Dual Specific Protein Phosphatase 1 (DUSP1), Nuclear Hormone Receptor 38 (NHR38), Heat Shock Protein 1 (HSP 72 KDa), Myelocytomatosis oncogene homologue (Mych), Growth arrest and DNA damage inducible alpha a (GADD 45aa) and Mitogen Activated Protein Kinase 4 (MAP2K4). This study contributes to unravelling the intricate relationship between chronic stress, cortisol, and the MAPK pathway in aquaculture, providing insights crucial for optimizing fish welfare and production.
Signaling pathway evaluation of leading ATRi, PARPi and CDK7i cancer compounds targeting the DNA Damage Response using Causal Inference
Authors: Truter Nina , Bergh Wikus , van den Heever Martine , Horn Shade , Shaw Klarissa , Leggate Dan , Wilkie Neil , Singh Raminderpal
Published: February 2024

Introduction: There are many cancer drugs in development which target the DNA damage response (DDR), following early successes of drugs such as olaparib. However, various challenges to the success of these inhibitors exist, including the emergence of resistance, the identification of appropriate biomarkers to identify patients who will respond to treatment, as well as the identification of combination therapies that improve efficacy without a concomitant increase in toxicity. While the identification of biomarkers of resistance could aid in overcoming these challenges, current methods mostly generate lists of potential genes, proteins that display changes in cancer patients, without exposing the underlying, and often critical, mechanisms of resistance. Methods: We have developed the Adaptable Large-Scale Causal Analysis (ALaSCA) software platform, which applies Pearlian Causal Inference (PCI) techniques to specifically transcriptomic, proteomic and phenotypic multi-omics data. ALaSCA quantifies the causal contributions of different biological pathways to an outcome such as responsiveness to treatment. The strength of applying PCI to biological pathways lies in quantifying the causal contributions of targets, through their related pathways, to drug sensitivity - as opposed to merely enriching or grouping lists of genes into pathways. We applied ALaSCA to transcriptomic data for several different compounds related to three known inhibitor types that target DDR proteins: an ATR, a CDK7, and several PARP inhibitors. Our aim was to use causal methods to evaluate biological signaling pathways to identify resistance mechanisms that can be used for patient stratification and development of combination therapies in breast, ovarian and non-small cell lung cancer (NSCLC). Key findings: We observed that niraparib seems to have a different resistance mechanism than other PARP inhibitors in breast and NSCLC, which is driven by CDK1 as opposed to base excision or nucleotide excision repair. Additionally, CDK7 appears to be a significant driver of PARP inhibitor resistance, especially for niraparib, through predominantly the G2/M cell cycle phase and to a lesser extent nucleotide excision repair in breast and ovarian cancer, but not in NSCLC. Lastly, we identified that genes from the homologous recombination pathway drive resistance to AZD6738, an ATR inhibitor, in breast cancer, and that AZD6738 and irinotecan have differing resistance mechanisms in ovarian cancer, indicating the potential of combining these treatments. Next steps: Our findings demonstrate the potential of ALaSCA to generate interesting insights for treatments when applied to public data and well-known inhibitors. Partnership with industry drug discovery groups using proprietary data to rerun the above evaluations will further refine and confirm these findings.
Fingerprint localisation for fine-scale wildlife tracking using automated radio telemetry
Authors: Tyson Chris , Fragueira Rita , Sansano-Sansano Emilio , Yu Hui , Naguib Marc
Published: February 2024

1: Automated radio telemetry systems are among the most widely applicable method for tracking wildlife at fine spatiotemporal scales. These systems are increasingly applying large networks of simple receivers to detect radio signal strength (RSS) from radio tagged individuals. Analytical methods to derive position estimates using RSS localisation, however, are relatively underdeveloped in the field of wildlife tracking. Here, we apply approaches from indoor positioning systems to develop a new method, radio fingerprinting, for localizing radio tagged animals in structurally complex, outdoor environments. This method characterizes the RSS patterns at known locations to generate a radio map of the study area, which is then used to predict the location of new RSS patterns. 2: We conducted field tests to evaluate the localisation accuracy of radio fingerprinting relative to multilateration, a commonly used method for RSS localisation. To do so, we established an experimental receiver network covering multiple habitat types and compared the localisation accuracy of radio fingerprinting to multilateration. Additionally, we evaluated how a variety of features characteristic of typical tracking datasets affected the accuracy of both methods. 3: While both methods had a similar median error (~30 m), the fingerprint localisation method offered several advantages over multilateration. Multilateration localisation estimates were highly affected by missed detections from the nearest receiver to the test point, which occurred in 30% of cases. In these cases, the median error was 97 m, over a 3-fold increase. Distance to the nearest receiver also biased multilateration estimates with error increasing as the distance increased. Additionally, errors from multilateration estimates were higher in more densely vegetated areas. In contrast, fingerprinting position estimates were largely robust to each of these scenarios. 4: Automated radio telemetry enables the fine-scale, continuous tracking of range-resident animals. We present radio fingerprinting as a localisation method in outdoor environments where standard localisation methods may be inadequate. This approach can be applied to any automated radio telemetry hardware and to any study system where a radio map can be generated.
Arabidopsis thaliana RHAMNOSE 1 condensate formation drives UDP-rhamnose synthesis
Authors: Field Sterling , Dorone Yanniv , Dwyer Will P. , Cox Jack A. , Raba Dan , Froehlich John , Blea Madison , Carmo Olivia M.S. , Wallace Ian S. , Hastings Renee , Boeynaems Steven , Rhee Seung Y.
Published: February 2024

Rhamnose is an essential component of the plant cell wall and is synthesized from uridine diphosphate (UDP)-glucose by the RHAMNOSE1 (RHM1) enzyme. RHM1 localizes to biomolecular condensates in plants, but their identity, formation, and function remain elusive. Combining live imaging, genetics, and biochemical approaches in Arabidopsis and heterologous systems, we show that RHM1 alone is sufficient to form enzymatically active condensates, which we name rhamnosomes. Rhamnosome formation is required for UDP-rhamnose synthesis and organ development. Overall, our study demonstrates a novel role for biomolecular condensation in metabolism and organismal development, and provides further support for how organisms have harnessed this biophysical process to regulate small molecule metabolism.
Jianpi Jiedu Recipe inhibits proliferation through reactive oxygen species-induced incomplete autophagy and reduces PD-L1 expression in colon cancer
Authors: Cheng Lingling , Xu Liangfeng , Yuan Hua , Zhao Qihao , Yue Wei , Ma Shuang , Wu Xiaojing , Gu Dandan , Sun Yurong , Shi Haifeng , Xu Jianlin
Published: February 2024

Abstract: Background: Jianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. Methodology: CCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. Xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. Results: JPJDR has a good inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1.Meanwhile, JPJDR can exert a good therapeutic effect in xenograft tumor mice. Conclusion: JPJDR is a low-toxic and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be through inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.
Integrative phylogenetic analysis of the genus Episoriculus (Mammalia: Eulipotyphla: Soricidae)
Authors: Liu Yingxun , Wang Xuming , Wan Tao , Liao Rui , Chen Shunde , Liu Shaoying , Yue Bisong
Published: February 2024

Shrews in the genus Episoriculus are among the least-known mammals in China, where representatives occur mainly in the Himalayan and Hengduan mountains. We sequence one mitochondrial and three nuclear genes from 77 individuals referable to this genus, collect morphometric data for five shape and 11 skull measurements from 56 specimens, and use museum collections and GenBank sequences to analyze phylogenetic relationships between this and related genera in an integrated molecular and morphometric approach. Whereas historically anywhere from two to eight species have been recognized in this genus, we conclude that six (E. baileyi, E. caudatus, E. leucops, E. macrurus, E. sacratus, E. soluensis) are valid. We dissent from recent systematic reviews of this genus and regard E. sacratus to be a valid taxon, E. umbrinus to be a subspecies of E. caudatus, and transfer E. fumidus to Pseudosoriculus. Our record of E. soluensis is the first for China, and expands the previously recognized distribution of this taxon from Nepal and NE India into the adjacent Yadong and Nyalam counties. One further undescribed Episoriculus taxon may exist in Tibet.
Matching provides efficient decisions
Authors: Kubanek Jan
Published: February 2024

How humans and animals distribute their behavior across choice options has been of key interest to economics, psychology, ecology, and related fields. Neoclassical and behavioral economics have provided prescriptions for how decision-makers can maximize their reward or utility, but these formalisms are used by decision-makers rarely. Instead, individuals allocate their behavior in proportion to the worth of their options, a phenomenon captured by the generalized matching law. Why biological decision-makers adopt this strategy has been unclear. To provide insight into this issue, this article evaluates the performance of matching across a broad spectrum of decision situations, using simulations. Matching is found to attain a high or near-optimal gain, and the strategy achieves this level of performance following a single evaluation of the decision options. Thus, matching provides highly efficient decisions across a wide range of choice environments. This result offers a quantitative explanation for the broad adoption of matching by biological decision-makers.
Taurine/chenodeoxycholic acid ratio as a circulating biomarker of insidious vitamin B12 deficiency in humans
Authors: Baghel Madhu , Shi Sting L. , Patel Himani , Velagapudi Vidya , Ali Abdullah M. , Yadav Vijay K.
Published: February 2024

Deficiency of vitamin B12 (B12), an essential water-soluble vitamin, leads to irreversible neurological damage, osteoporosis, cardiovascular diseases, and anemia. Clinical tests to detect B12 deficiency lack specificity and sensitivity. B12 deficiency is thus insidious because progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of B12-deficient versus control individuals, we set out to identify biomarker(s) of B12 deficiency. Metabolomic profiling identified 77 metabolites, and Partial least squares discriminant-analysis (PLS-DA) and hierarchical clustering analysis (HCA) showed a differential abundance in B12-deficient sera of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin, and glycocholic acid. Random forest (RF) multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict B12 deficiency. Mechanistically, B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell identifying a downregulation of methionine, taurine, urea cycle, and nucleotide metabolism, and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of B12 deficiency in humans and elucidate cellular metabolic pathways regulated by B12 deficiency.
LIVED EXPERIENCES OF MOTHERS WITH PERIPARTUM CARDIOMYOPATHY
Authors: Mukona Doreen , Tsiko Barbara , Zvinavashe Mathilda
Published: February 2024

Peripartum cardiomyopathy is known to occur more commonly in African women or those of African descent, with potentially devastating consequences.  The purpose of this study was to explore the lived experiences of women with post-partum cardiomyopathy. A phenomenological approach was used. The study was conducted with 6 women with a confirmed diagnosis of peri-partum cardiomyopathy who were registered with the Parirenyatwa Group of Hospitals Cardiac clinic.  Excluded from the study, due to compromised autonomy, were the mentally ill, critically ill, and the institutionalized.  Participants were selected as they came for routine management. In-depth interviews, following semi structured questionnaires, were conducted. All participants gave informed consent, and the study was conducted according to the requirements of the Declaration of Helsinki. Interviews were held in a private room and filled in questionnaires and detailed notes were anonymized and kept in a lockable cupboard to which the researchers had sole access. Manual thematic analysis was used to analyze the data and it was presented in themes, subthemes, and codes. The stages of thematic analysis followed were data organization, familiarization, transcription, coding, identifying themes, indexing, reviewing themes, displaying, and reporting. Trustworthiness was ensured by observing credibility, dependability, confirmability, and transferability. Three major themes namely: experience on diagnosis, psychosocial tension and supporting factors were identified. Women diagnosed with peripartum cardiomyopathy experience physical, psychological, and emotional stress. Psychosocial support is very vital in the management of peripartum cardiomyopathy.
A Machine Learning Classification of Individuals with Mild Cognitive Impairment into Variants from Writing
Authors: Kim Hana , Hillis Argye , Themistocleous Charalambos
Published: February 2024

Introduction

Individuals with Mild Cognitive Impairment (MCI), a transitional stage between cognitively healthy aging and dementia, are characterized by subtle neurocognitive changes. Clinically, they can be grouped into two main variants, namely into patients with amnestic MCI (aMCI) and non-amnestic MCI (naMCI). The distinction of the two variants is known to be clinically significant as they exhibit different progression rates to dementia. However, it has been particularly challenging to classify the two variants robustly. Recent research indicates that linguistic changes may manifest as one of the early indicators of pathology. Therefore, we focused on MCI’s discourse-level writing samples in this study. We hypothesized that a written picture description task can provide information that can be used as an ecological, cost-effective classification system between the two variants.

Methods

We included one hundred sixty-nine individuals diagnosed with either aMCI or naMCI who received neurophysiological evaluations in addition to a short-written picture description task. Natural Language Processing (NLP) and BERT pre-trained Language Models were utilized to analyze the writing samples.

Results

We showed that the written picture description task provided 90% overall classification accuracy for the best classification models, which performs better than cognitive measures.

Discussion

Written discourses analyzed the AI models can automatically assess individuals with aMCI and naMCI and facilitate diagnosis, prognosis, therapy planning, and evaluation.
Dynamic Dark Root Chamber: Advancing non-invasive phenotyping of roots kept in darkness using infrared imaging
Authors: Pree Simon , Kashkan Ivan , Retzer Katarzyna
Published: February 2024

Root phenotyping is a challenging task that would require monitoring root growth in soil under dark conditions to mimic natural conditions, while allowing the shoot to grow in light. Most existing methods involve exposing the roots to light, which substantially alters their growth and function. In this paper, we present an improved imaging system that can overcome this limitation of experiments performed in laboratories. The Dynamic Dark Root imaging Chamber (DDrC) enables continuous monitoring and image acquisition to track the dynamic development of root architecture under controlled growth conditions. Our imaging system is based on a Raspberry Pi camera module and infrared LEDs, which do not induce any stress responses in the roots. The DDrC setup is simple, affordable, and suitable for dynamic phenotyping experiments. We provide a detailed tutorial for the assembly and adjustment of the imaging chamber. We conclude that our system is a valuable tool for studying the genetic and environmental factors that affect the root system architecture and development, and for identifying the root traits that are related to plant adaptation and performance.