bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Intermittent Hypoxia with Hypercapnia has Complex effects on Phrenic Long-Term Facilitation that Depend on Delivery in the Rest versus Active Phase in Rats
Authors: L.E. Butenas Alec , B. Marciante Alexandria , Burrowes Kayla , S. Mitchell Gordon 
Published: May 2024

Exploration of mechanisms giving rise to respiratory motor plasticity, such as phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH), has inspired new therapeutic approaches to treat individuals affected by conditions such as spinal cord injury or other clinical disorders. One key step in the translation between rodent models and humans is the apparent need for hypercapnia (either baseline or within hypoxic episodes) during AIH. Whereas AIH consisting of 15, 1-minute hypoxic episodes (1-minute intervals) elicits robust pLTF in rats, similar protocols have minimal impact in humans—unless PaCO2 levels are increased. Although prior studies report that elevated baseline CO2 actually impairs AIH-induced pLTF in rats, the impact of hypercapnia within hypoxic episodes is not known. Thus, we compared AIH with and without concurrent hypercapnia (AIH versus AIHH) on pLTF in anesthetized rats. Since our laboratory recently reported profound time-of-day effects on pLTF magnitude and/or mechanisms, we also compared AIH versus AIHH-induced pLTF during the daily rest and active phase. We hypothesized that AIHH would enhance pLTF versus AIH in both phases, suggesting it may be a more effective intervention to elicit respiratory motor plasticity and respiratory rehabilitation. pLTF was assessed in anesthetized, paralyzed, vagotomized and ventilated male Sprague-Dawley rats ( n=6 per group) exposed to moderate AIH (arterial PO2 = 40-55mmHg) consisting of: 1) 15, 1-minute hypoxic episodes with concurrent hypercapnia (arterial PCO2 ~50mmHg) or 15, 1-minute episodes of isocapnic hypoxia (baseline arterial PCO2 ~2 mmHg above the recruitment threshold; ~40-42 mmHg). We also compared AIHH versus AIH during the active phase using prior published data (AIHH, n = 4; AIH, n = 7; data from Nair et al., Function, 2023 and Marciante et al., Function, 2023, respectively). Contrary to our hypothesis, pLTF was attenuated 90 minutes post-AIHH (37±8%) versus AIH (83±4%; p<0.001) in the rest phase. In striking contrast, during the active phase, pLTF was greater with AIHH (60±11%) versus AIH (30±4%; P=0.012). These unexpected outcomes demonstrate that time of day (or the rest/active phase) must be considered before adding hypercapnia to an AIH protocol. Although the mechanisms of this difference remain unclear, our results make clear that there is still a great deal to learn about mechanisms of AIH-induced respiratory motor plasticity, including the complex interplay between hypoxia, hypercapnia and their impact on pLTF. Supported by: NIH R01 HL147554 & R01 HL148030 (PI: G. Mitchell). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Establishing the SHort course In transFerable skills Training (SHIFT) Program
Authors: Woods Letha , Lindsey Merry 
Published: May 2024

While Ph.D. programs prepare graduate students to perform biomedical research, a defined systematic training program for transferable skills is generally lacking. When provided, this training is often informal, unstructured, or inconsistent. Therefore, there is a need to provide critical skills in marketing, relationship building, project management, and budgeting to prepare trainees to navigate into a productive, engaging, and rewarding biomedical research career. To address this gap in training, the graduate school at Meharry Medical College has developed the SH ort Course I n trans F erable skills T raining (SHIFT) Program, a one-year professional development program accessible to graduate students in the Southeast United States. The SHIFT Program has been launched to equip trainees with skills essential for success in all biomedical science careers. PhD Students between years one and two in their graduate program will be taught the primary constituents of career management through the use of four training modules. In Module I, students will complete self-assessments and be assigned to a small peer-mentoring team of six students with two mentors. Module II will consist of a 5-day workshop that encompasses instruction on the transferable skills identified as essential for career success. Module III will entail monthly interactive discussions over a 6-month period involving case study review and mentor-guided discussions to further reinforce skills learned. In Module IV, students will compile the information learned from Modules I-III to develop an Individual Development Plan that incorporates 3-5 specific, measurable, attainable, relevant, and time-based (SMART) career goals. Collectively, the SHIFT Program will allow participants to train, practice, and refresh skills, empowering them to navigate career transitions and obtain success in the career of their choice. NIH GM151274 and VA I01BX000505. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Recovery of Ventilatory and Metabolic Responses to Hypoxia after Chronic Hypoxia in Neonatal Rats
Authors: Kinnally Annie , Lee Darya , Bavis Ryan 
Published: May 2024

Chronic hypoxia (CH) from birth blunts the hypoxic ventilatory response (HVR) in newborn rats, but there is conflicting evidence as to whether (or how quickly) the HVR recovers after these rats are returned to room air. In this study, Sprague-Dawley rats were exposed to either 21% O2 (Control) or 12% O2 (CH) for the first 3 postnatal days. Breathing and metabolism were studied using head-body plethysmography and respirometry immediately after the 3 days of CH (i.e., at P3) or after 1, 4-5, or 7 days of recovery in room air (i.e., at P4, P7-8, or P10). The early phase of the HVR was blunted in CH rats at P3 (13.7± 2.3 vs. 30.6±3.4 % increase from baseline during 12% O2), and the HVR was more biphasic in CH rats after 1 day of recovery. However, no significant differences in the HVR were observed between treatment groups after 3-4 or 7 days of recovery. Males and females showed similar patterns. Changes in ventilation during hypoxia were strongly biphasic in the younger age groups: ventilation increased initially, but this was followed by a gradual decline in ventilation towards or below baseline levels. However, when accounting for metabolic depression, all age groups continued to hyperventilate during the late phase of the HVR [i.e., the ratio of ventilation to CO2 production (CO2 convection requirement) remained elevated relative to baseline values]. The CO2 convection requirement response to hypoxia did not differ between treatment groups during the late phase of the HVR at any age, but metabolism and CO2 convection requirement could not be determined during the early phase of the HVR due to non-steady state conditions. In conclusion, 3 days of CH produces only a transient blunting of the HVR in newborn rats. Longer CH exposures may be required to elicit persistent changes in the HVR or, alternatively, this plasticity may not be revealed until after puberty. Supported by NIH grant P20 GM-103423 (Maine INBRE). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Restoring Cardiac Health: Abstinence Leads to Recovery from Alcohol-Induced Cardiomyopathy
Authors: Edavettal Joshua , Harris Nicholas , Cohen Sarah , Paloczi Janos , Bysani Chandrasekar , Gardner Jason D. 
Published: May 2024

Chronic drinking can lead to alcohol-induced cardiomyopathy (ACM), a disease currently without a cure. Using a mouse model of ACM, we observed significant cardiac dysfunction after 30 days. Our study’s goal was to investigate the potential restoration of cardiac function following a period of abstinence. Our hypothesis is that abstinence can lead to an observable recovery in overall cardiac function. C57BL/6J mice were given the Lieber-DeCarli liquid diet with 5% ethanol for 30 days, with two ethanol binges on days 10 and 30 (5 g/kg). After the 30-day ethanol exposure, the mice were transitioned to an ethanol-free diet for an additional 30 days. Left ventricular catheterization and echocardiography were conducted at the 30- and 60-day timepoints. 30 days of ethanol consumption led to significant decreases in both systolic and diastolic function. However, following a period of alcohol abstinence, there was a marked improvement. Specifically, the 30-day ethanol mice exhibited increases in stroke work and dP/dt max after 30 days of abstinence; stroke work increased from 1119 ± 89 mmHg*μL to 2032 ± 139 mmHg*μL (p < 0.0001), and dP/dt max increased from 8054 ± 664 mmHg/s to 11967 ± 449 mmHg/s (p < 0.001). Diastolic function also improved; dP/dt min from -7711 ± 561 mmHg/s to -10202 ± 594 (p < 0.01). We also found a significant increase in load-independent cardiac contractility, i.e. the slope of end systolic pressure volume relation: 6.89 ± 0.6 mmHg/μL to 10.59 ± 1.57 mmHg/μL (p < 0.05). In conclusion, abstinence after chronic ethanol exposure can lead to a restoration of cardiac function in C57BL/6J mice. This model parallels limited clinical data on abstinence and will allow us to study the underlying mechanisms responsible for the restoration of function. R21AA029747 (JG, CB), F30AA030472 (JE). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Analysis of Lysine Metabolism in a Rat Model of Type 2 Diabetes Reveals Modulation of Endocytosis and Glucose Metabolism
Authors: Tan Yifan , Dissanayake Lashodya , Kravtsova Olha , Demir Fatih , Levchenko Vladislav , Staruschenko Alexander , Rinschen Markus 
Published: May 2024

Lysine is an essential amino acid that serves as a building block for proteins and plays a role in metabolic processes. While a recent study provided evidence that lysine is beneficial for hypertension-associated kidney disease, possibly through inhibiting renal tubular reabsorption and forming new lysine conjugates, knowledge about the role of lysine in diabetic nephropathy (DN) is rudimentary. Therefore, the aim of the study was to investigate the role of lysine in kidney function in the setting of DN and its underlying mechanisms. We hypothesized that lysine may impact the kidneys in the following ways: 1) by mediating protein endocytosis in proximal tubules; 2) by altering protein abundance in the kidneys and other organs; and 3) by disrupting metabolic pathways through the formation of conjugates or degradation products. We investigated the effects of lysine on proximal tubule endocytosis and other organs using proteomic approaches and studied changes in lysine conjugates and metabolic products using targeted metabolomics. The results of urinary proteomics suggested that lysine’s impact on endocytosis may be associated with the inhibition of megalin and cubilin. Furthermore, lysine affected proteins related to glucose metabolism. Subsequently, we proceeded to investigate the influence of lysine on various organs in Type 2 Diabetic Nephropathy (T2DN) rats. Gene Ontology (GO) enrichment revealed that lysine exerts tissue-specific effects on different organs, with pathways enriched in the kidney including phagocytosis and enzyme inhibitor activity. Additionally, within the kidney, the lysine-treated group showed downregulation of glycolysis-related enzymes. The metabolomics results showed that lysine leads to a decrease in glucose and an increase in fructose 1,6-bisphosphate, while also resulting in an upregulation of related metabolites in the tricarboxylic acid cycle (TCA cycle). Our findings showed changes in the protein composition involved in lysine-mediated endocytosis and the impact of lysine on glucose metabolism enzymes and metabolites. The specific molecular mechanisms are still under investigation. R01 DK135644 and I01 BX004024 (to AS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Impact of Trade Liberalisation and MSME Classification on Productivity of Indian Manufacturing Firms
Authors: Mukherjee Subhadip , Chanda Rupa 
Published: May 2024

This article examines the effects of tariff and non-tariff reductions on firm-level productivity of large as well as Micro, Small and Medium Enterprises (MSMEs) in India’s manufacturing sector for the 1999–2009 period. We calculate input and final goods tariffs, effective rates of protection and non-tariff barriers (NTBs) for broad product groups using information from India’s Exim Policy of 1997–2003 and 2004–2009 to examine this impact. We use a balanced as well as unbalanced firm-level panel data set, while accounting for firm, industry, state and time-specific factors. By using fixed effect models and Heckman’s two-step estimation procedure, we find that trade liberalisation is associated with improved firm-level productivity for large firms but not in the case of MSMEs. We posit that this might be due to the relative disadvantages that Indian MSMEs face which prevent them from benefiting from trade liberalisation. We also find that productivity gains arising from the sourcing of imported inputs have been greater than those arising from increased product competition and that NTB liberalisation has had a greater impact compared to tariff liberalisation on firm-level productivity. Changes in MSME legislation and the classification of firms are also found to have a bearing on firm performance. Our study contributes to the literature by confirming the need to focus specifically on constraints faced by MSMEs if they are to benefit from trade liberalisation. It highlights the importance of liberalising trade in intermediates as well as the role of MSME classification in enabling productivity gains. JEL Codes: L6, D24, L1, F13
DOLPHIN: A Mixed-Methods Study of a Parenting App to Nurture the First Two Years of Life in the Indian Context
Authors: Sravanti Lakshmi , Mundkur Nandini 
Published: May 2024

Background: The first two years of life are critical for brain development. Experiences and exposures during this period can have long-term effects on an individual’s health. Therefore, we aim to develop a program for new parents in the Indian context to help them understand their developing infant’s needs and provide the best possible care grounded in traditional practices to ensure healthy developmental outcomes. Materials and Methods: The program was developed using the exploratory–confirmatory framework grounded in qualitative methods—(a) collection of empiric evidence base by conducting a thorough literature review, (b) tacit experience, and (c) focus group discussions with relevant stakeholders. Picture-based content (one picture per day for two years) was created, and the program was expert-validated. A web-based application was developed to make it available to parents, and the program was translated into three regional languages to improve its reach. A telephonic user feedback survey was carried out, and descriptive statistics were used to present the findings from the survey. Results: DOLPHIN stands for “Developing Opportunities of Learning for Parents to Help Infant Nurture.” Over 600 parents accessed the program. Feedback is positive in the domains of parental satisfaction and user-friendliness. Discussion: The program primarily focuses on ensuring appropriate sensorimotor stimulation and meeting the socioemotional needs of the growing infant through the first two years, emphasizing healthy nutrition and hygiene to ensure holistic development. Therefore, its approach is health-promotive and disease-preventive. It incorporates traditional child-rearing practices of India rich in stimulation, promoting secure attachment, and incidental learning: “readiness.” Conclusion: The DOLPHIN program demonstrates a promising approach to supporting new parents in nurturing their infants during the critical first two years of life. With positive feedback and a focus on traditional practices and evidence-based content, it holds potential as a health-promotive and preventive intervention for holistic child development in the Indian context.
Aqueous humor proteomics analyzed by bioinformatics and machine learning in PDR cases versus controls
Authors: Wang Tan , Chen Huan , Li Ningning , Zhang Bao , Min Hanyi 
Published: May 2024

Abstract
Background
To comprehend the complexities of pathophysiological mechanisms and molecular events that contribute to proliferative diabetic retinopathy (PDR) and evaluate the diagnostic value of aqueous humor (AH) in monitoring the onset of PDR.

Methods
A cohort containing 16 PDR and 10 cataract patients and another validation cohort containing 8 PDR and 4 cataract patients were studied. AH was collected and subjected to proteomics analyses. Bioinformatics analysis and a machine learning-based pipeline called inference of biomolecular combinations with minimal bias were used to explore the functional relevance, hub proteins, and biomarkers.

Results
Deep profiling of AH proteomes revealed several insights. First, the combination of SIAE, SEMA7A, GNS, and IGKV3D-15 and the combination of ATP6AP1, SPARCL1, and SERPINA7 could serve as surrogate protein biomarkers for monitoring PDR progression. Second, ALB, FN1, ACTB, SERPINA1, C3, and VTN acted as hub proteins in the profiling of AH proteomes. SERPINA1 was the protein with the highest correlation coefficient not only for BCVA but also for the duration of diabetes. Third, “Complement and coagulation cascades” was an important pathway for PDR development.

Conclusions
AH proteomics provides stable and accurate biomarkers for early warning and diagnosis of PDR. This study provides a deep understanding of the molecular mechanisms of PDR and a rich resource for optimizing PDR management.
Storz professional image enhancement system (SPECTRA A) enhancing detection of carcinoma urinary bladder by white light cystoscopy
Authors: Gnyawali Diwas , Sigdel Prem Raj , Rai Bipendra D. K. , Chapagain Suman , Gyawali Prem Raj 
Published: May 2024

Abstract
Background
SPECTRA A filters red light from white light through software to create contrast for better tissue visualization and light penetration. We aim to find whether the detection rate of bladder cancer is enhanced by SPECTRA A in adjunct to White Light Cystoscopy (WLC).

Methods
This was a prospective observational study among 66 patients in the Department of Urology and Kidney Transplant Surgery, Tribhuvan University Teaching Hospital. All patients undergoing TURBT for suspected/diagnosed bladder tumor were evaluated with WL, followed by SPECTRA A mode, and findings were recorded using visual bladder mapping. Resection of the tumor was done on WL, margins were again reevaluated using SPECTRA A mode, and a biopsy was taken in cases of suspicious findings confirmed on SPECTRA A. Tumor detection rate (sensitivity), extra lesion detection, false positive rate, and margin status were evaluated through 2 × 2 tables, McNemar chi-square test on patient level as well as lesion level.

Results
A total of 64 patients were included in the study. The mean age was 62.20 ± 13.98 with a sex ratio of M:F 4.3:1. SPECTRA A and WL had a detection rate of 95.33% and 78.80% (p = 0.001), respectively, and positive biopsy of detected lesions was 78.8% and 84.13% (p = 0.041), respectively, for SPECTRA A and WL. The false positive rate of SPECTRA A and WL was 21.19% and 15.86% (p = 0.006), respectively, whereas the false negative rate was 4% and 19.2% (p = 0.001), respectively. The number of extra lesions detected by SPECTRA A was 39, out of which 29 were histologically proven tumors.

Conclusion
SPECTRA A enhances the detection rate of bladder cancer when used with WL. We can increase the detection of bladder cancer by using a combination of white light and SPECTRA A.
Effect of novel anti-tumor and anti-angiogenesis drug taurolactone on angiogenic factor AGGF1 and angiogenesis mimicry in patients with hepatocellular carcinoma
Authors: Liu Shaoping , Wei Yinzhi , Nie Lei , Tang Ze , Lu Qi , Liang Qun 
Published: May 2024

Abstract
Objective
Our study was to investigate the impact of taurolactone, a novel anti-tumor and anti-angiogenic drug, on AGGF1, an angiogenic factor, and angiogenesis mimicry in patients diagnosed with hepatocellular carcinoma (HCC).

Methods
A total of 120 HCC patients were enrolled from the Department of Oncology and Hepatobiliary Surgery at our hospital between May 2021 and December 2022. HCC diagnoses were confirmed through imaging or tissue biopsy for all patients. The age of patients ranged from 37 to 72 years, with an average age of 64.29 ± 4.58 years. These participants were divided equally into two groups: the control group and the observation group, each consisting of 60 individuals. While the control group received standard drug treatment, the observation group was administered taurolactone treatment. Before being included in the study, all participants or their legal representatives provided signed informed consent. Patient demographic information was collected through a questionnaire survey. ELISA was used to measure the levels of VEGF and AGGF1 in patients following treatment. Western blot was applied to assess the protein expression of PDGF, Angiopoietin, and AGGF1. MRI imaging technology was utilized to assess the perfusion characteristics of tumor blood vessels in patients. Tumor vessel density was compared between patients using ultrasonography. We also conducted a comparison between the two groups in terms of progression-free survival and overall survival.

Results
General patient information between the two groups showed no significant differences (P > 0.05). Of note, the observation group exhibited greatly lower levels of VEGF and AGGF1 compared to the control group (P < 0.05). Moreover, the levels of PDGF, Angiopoietin, and AGGF1 protein expression were significantly reduced in the observation group compared to the control group (P < 0.05). In terms of tumor perfusion, the observation group displayed lower average and maximum perfusion volumes in tumor blood vessels compared to the control group (P < 0.05). Additionally, the observation group demonstrated delayed peak times and arrival times of tumor blood vessels in comparison to the control group (P < 0.05). Furthermore, the density of tumor blood vessels was notably lower in the observation group compared to the control group (P < 0.05). Patients in the observation group had longer progression-free survival and overall survival than the control group (P < 0.05).

Conclusion
In HCC patients, our study highlighted the potential efficacy of taurolactone treatment as it effectively inhibited angiogenic factors and angiogenesis mimicry, ultimately leading to an improved prognosis for these patients.