bluuebunny/crossref_metadata_2025_split huggingface dataset:
A perplexing case report of concomitant multiple sclerosis and myasthenia gravis
Authors: Al-Mollah Mustafa , Hussein Moaiad , Qiqieh Jamil , Sidhu Hardeep , Ryalat Nosaiba , Bahou Yacoub 
Published: May 2024

Introduction and importance:
The co-occurrence of multiple sclerosis (MS) and myasthenia gravis (MG) within the Middle East and North African Region (MENA) has been scarcely reported in current literature. This rare case report explores the pathophysiological mechanisms and potential avenues of treatment modalities. Such insights can potentially facilitate the development of more efficacious and targeted treatment modalities and perhaps pave the way for disease prevention.

Case description:
Twenty-nine-year-old female patient presented with diplopia of two weeks duration associated with occasional blurred vision in the left eye. On physical examination, she was discovered to have marked left eye ptosis. A visual evoked potential (VEP) test was performed, which revealed asymmetrical delay. MRI imaging revealed a few white matter hyperintense foci noted at both periventricular regions and the corpus callosum with the characteristic appearance of Dawson’s fingers, and thus MS was diagnosed. An anti-acetylcholine receptor antibody test returned positive, confirming the diagnosis of concurrent MG.

Clinical discussion:
Proposed pathophysiological mechanisms underlying the concurrent manifestation of both diseases include, among others, the involvement of HLA haplotype and non-HLA genotypes, as well as the immunogenetic influence of specific transcription factors. Notable HLA haplotype genes include DRB1 and HLA-DQ5 genes. In contrast, non-HLA genes include the interleukin-4 receptor (IL4RA) and factor forkhead box P3 (FOXP3).

Conclusion:
Considering the similar immunological background of the two diseases, ideally, a single therapeutic modality could be used for management. This will hopefully simplify the patient’s treatment regimen and may ultimately reduce the treatment cost and patient burden.
Reliability of Publicly Available Digital Endoscopes in Otolaryngology: A Pilot Study
Authors: McWilliams Michael P. , Quinn Kevin , Lee Lawrance , Manzoor Nauman F. , Coelho Daniel H. 
Published: May 2024

Objective:
To compare the utility, accuracy, and confidence of an inexpensive, commercially available endoscope (not specifically designed for medical use) with traditional methods in the diagnosis of otologic conditions.

Study Design:
This is a prospective study.

Methods:
Following institutional review board approval, patients were recruited from a tertiary university-based otology/neurotology clinic. Complete history and physical were obtained by the resident, including both traditional handheld otoscopy and image captured from a commercially available digital endoscopic device (AnyKit Digital Otoscope with 4.5-inch screen). The patient was then presented to the attending without the endoscopic images and a putative diagnosis was made. The endoscopic images were then shown and the putative diagnosis was affirmed or rejected. The attending then examined the patient and determined the final diagnosis using the microscope. Data collected included resident year, resident and attending diagnosis before and after digital-otoscopic images, confidence in diagnosis (1–5 scale), and agreement between the initial putative diagnosis and the final diagnosis. Noninferiority testing was calculated using inter-rater agreement between digital-otoscopic and final diagnoses. Differences between resident and attending confidence were analyzed. A power analysis was performed and the sample size was calculated a priori.

Results:
A total of 62 participants (114 ears examinations) were enrolled. Cohen’s kappa coefficient showed very high agreement between both resident and attending digital-otoscopic and final diagnosis (kappa = 0.868 and 0.882, respectively) suggesting noninferiority between the digital otoscope and the final diagnosis. There was no significant difference between attending confidence in diagnosis following resident presentation versus attending confidence in diagnosis after reviewing images (4.65 vs 4.61, P = 0.701). Average resident confidence in digital-otoscopic diagnosis remained above 4.2 throughout the study.

Conclusion:
Inexpensive and readily available digital endoscopes are not inferior to the traditional methods of resident-attending consultation and may provide some substantial benefits. Such devices have the potential to enhance both patient care and resident education when faculty are not immediately available (ie, inpatient and emergency room consults) and improve patient-initiated communications.
Randomized Controlled Trial of 60 minutes for Health With Rapid Antiretroviral Therapy to Reengage Persons With HIV Who Are Out of Care
Authors: Martin Thomas C. S. , Smith Laramie R. , Anderson Christy , Little Susan J. 
Published: May 2024

Background:
Many persons with HIV remain out of care (PWH-OOC). We evaluated InstaCare, a complex intervention integrating the brief behavioral intervention 60 minutes for Health with the rapid restart of antiretroviral therapy (rapid ART).

Setting:
Prospective open-label randomized controlled trial among PWH-OOC in San Diego, USA.

Methods:
PWH-OOC were randomized 1:1 to InstaCare or a time-and-attention control integrating a diet-and-nutrition behavioral intervention also with rapid ART initiation (restart ≤7 days from enrollment). All participants had access to support services (free transport, HIV peer navigation, adherence counseling, and linkage to care) and primary care services (mental health, case management, social work, medication-assisted treatment, and specialist pharmacy). The primary outcomes were viral suppression (<50 copies/mL) and re-engagement with care (≥2 HIV care visits >90 days apart) by 24 weeks. Outcomes were reported on an intention-to-treat basis.

Results:
Between November 2020 and August 2022, 52 PWH-OOC were enrolled. Baseline substance use in the preceding month (49%), unstable housing (51%), moderate/severe depression (49%), and moderate/severe anxiety (41.7%) were prevalent. Rapid ART was provided for all participants. At week 24, the proportion with HIV viral load <50 copies/mL was 37.3% (19/51) (InstaCare 28.0%, control 46.2%, P = 0.25). Fourteen (27.5%) were engaged with care (InstaCare 7/25 [28.0%], control 7/26 [26.9%], P = 1.00). Most participants (94%) reported low or very low emotional distress associated with rapid ART. Study lost to follow-up by week 24 was high (23/51, 45%).

Conclusions:
The InstaCare complex intervention did not improve viral suppression or reengagement with care among PWH-OOC. Investigation of high-intensity, individually adapted interventions is needed among PWH-OOC.
Preoperative Risk Assessment of Early Kidney Graft Loss
Authors: Eerola Verner , Sallinen Ville , Lyden Grace , Snyder Jon , Lempinen Marko , Helanterä Ilkka 
Published: May 2024

Background.
A large proportion of potential organ donors are not utilized for kidney transplantation out of risk of early allograft loss because of donor-related characteristics. These can be summarized using kidney donor profile index (KDPI). Because KDPI affects the choice of the recipient, the predictive ability of KDPI is tied to recipient attributes. These have been questioned to explain most of the predictive ability of KDPI. This study aims to quantify the effect of the donor on early graft loss (EGL) by accounting for nonrandom allocation.

Methods.
This study included patients undergoing kidney transplantation from deceased donors between 2014 and 2020 from the Scientific Registry of Transplantation Recipients. EGL, defined as a return to dialysis or retransplantation during the first posttransplant year, was the primary endpoint. Nonrandom allocation and donor–recipient matching by KDPI necessitated the use of inverse probability treatment weighting, which served to assess the effect of KDPI and mitigate selection bias in a weighted Cox regression model.

Results.
The study comprised 89 290 transplantations in 88 720 individual patients. Inverse probability treatment weighting resulted in a good balance of recipient covariates across values of continuous KDPI. Weighted analysis showed KDPI to be a significant predictor for short-term outcomes. A comparable (in terms of age, time on dialysis, previous transplants, gender, diabetes status, computed panel-reactive antibodies, and HLA mismatches) average recipient, receiving a kidney from a donor with KDPI 40–60 had a 3.5% risk of EGL increased to a risk of 7.5% if received a kidney from a KDPI >95 donor (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7). However, for all-cause survival KDPI was less influential.

Conclusions.
The predictive ability of KDPI does not stem from recipient confounding alone. In this large sample-sized study, modeling methods accounting for nonindependence of recipient selection verify graft quality to effectively predict short-term transplantation outcomes.
Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies
Authors: Mella Alberto , Lavacca Antonio , Dodoi Diana Teodora , Presta Roberto , Fop Fabrizio , Campagna Marco , Manzione Ana Maria , Dolla Caterina , Gallo Ester , Abbasciano Isabella , Gai Chiara , Camussi Giovanni , Barreca Antonella , Caorsi Cristiana , Giovinazzo Gloria , Biancone Luigi 
Published: May 2024

Background.
Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA+. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs.

Methods.
Single-center retrospective analysis of TG cases without anti-HLA DSAs (TG/DSA) treated with TCZ for chronic antibody-mediated rejection as first-line therapy evaluated through clinical, protocol biopsies, and gene expression analyses was included.

Results.
Differently from TG/DSA+, TG/DSA– showed a progressive reduction in the estimated glomerular filtration rate at 12 mo and after that with no significant modification in microvascular inflammation or C4d+. No upregulation in tight junction protein-1, aldo-keto reductase family 1 member C3, and calcium/calmodulin-dependent serine protein kinase, documented in TG/DSA+, was noted in post-TCZ biopsies. The reduction of microvascular inflammation was associated with natural killer-cell reduction in TG/DSA+, whereas TG/DSA– tends to maintain or increase periglomerular/interstitial infiltration.

Conclusions.
In the absence of anti-HLA DSAs, TG behavior seems not to be modified by IL-6 receptor blockade. These results are at variance with observational studies and previous trials with IL-6 inhibitors in TG associated with anti-HLA DSAs. These data may fuel the hypothesis of different mechanisms underlying TGs (including the potentially different roles of natural killer cells) and suggest carefully selecting patients with TG for clinical trials or off-label treatment based on their antidonor serologic status.
Deceased Donors With HIV in the Era of the HOPE Act: Referrals and Procurement
Authors: Liang Tao , Salas Jordan H. , Bowring Mary G. , Kusemiju Oyinkan , Barnaba Brittany , Wingler Matthew , McRann Deborah , Salama Alghidak , Wood R. Patrick , Massie Allan , Werbel William , Tobian Aaron A. R. , Segev Dorry L. , Durand Christine M. 
Published: May 2024

Background.
The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30–35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice.

Methods.
We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests.

Results.
From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001). Compared with HIV D+ without procurement, HIV D+ with procurement were younger (median age 36 versus 50 y), more commonly White (46% versus 36%), and more often had trauma-related deaths (29% versus 8%) (all P < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%).

Conclusions.
In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.
Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine Booster Doses in Kidney Transplant Recipients: Results of a 12-mo Follow-up From a Prospective Observational Study
Authors: Petr Vojtech , Zahradka Ivan , Modos Istvan , Roder Matej , Fialova Martina , Machkova Jana , Kabrtova Katerina , Hruba Petra , Magicova Maria , Slavcev Antonij , Striz Ilja , Viklicky Ondrej 
Published: May 2024

Background.
Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs.

Methods.
A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology.

Results.
Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19.

Conclusions.
Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).
Adipose microenvironment promotes hypersialylation of ovarian cancer cells
Authors: Fox Alexandra , Leonard Garry D. , Adzibolosu Nicholas , Wong Terrence , Tedja Roslyn , Sharma Sapna , Gogoi Radhika , Morris Robert , Mor Gil , Fehl Charlie , Alvero Ayesha B. 
Published: May 2024

AbstractSialylation, the addition of negatively charged sialic acid sugars to terminal ends of glycans, is upregulated in most cancers. Hypersialylation supports multiple pro-tumor mechanisms such as enhanced migration and invasion, resistance to apoptosis and immune evasion. A current gap in knowledge is the lack of understanding on how the tumor microenvironment regulates cancer cell sialylation. The adipose niche is a main component of most peritoneal cancers’ microenvironment. This includes ovarian cancer (OC), which causes most deaths from all gynecologic cancers. In this report, we demonstrate that the adipose microenvironment is a critical regulator of OC cell sialylation.In vitroadipose conditioning led to an increase in both ⍺2,3- and ⍺2,6-linked cell surface sialic acids in both human and mouse models of OC. Adipose-induced sialylation reprogramming was also observedin vivofrom intra-peritoneal OC tumors seeded in the adipose-rich omentum. Mechanistically, we observed upregulation of at least three sialyltransferases, ST3GAL1, ST6GAL1 and ST3GALNAC3. Hypersialylated OC cells consistently formed intra-peritoneal tumors in both immune-competent mice and immune-compromised athymic nude mice. In contrast, hyposiaylated OC cells persistently formed tumors only in athymic nude mice demonstrating that sialylation impacts OC tumor formation in an immune dependent manner. To our knowledge, this is the first demonstration of the effect of adipose microenvironment on OC tumor sialylation. Our results set the stage for translational applications targeting sialic acid pathways in OC and other peritoneal cancers.
Molecular counting of myosin force generators in growing filopodia
Authors: Fitz Gillian N. , Tyska Matthew J. 
Published: May 2024

ABSTRACTAnimal cells build actin-based surface protrusions to enable biological activities ranging from cell motility to mechanosensation to solute uptake. Long-standing models of protrusion growth suggest that actin filament polymerization provides the primary mechanical force for “pushing” the plasma membrane outward at the distal tip. Expanding on these actin-centric models, our recent studies used a chemically inducible system to establish that plasma membrane-bound myosin motors, which are abundant in protrusions and accumulate at the distal tips, can also power robust filopodial growth. How protrusion resident myosins coordinate with actin polymerization to drive elongation remains unclear, in part because the number of force generators and thus, the scale of their mechanical contributions remain undefined. To address this gap, we leveraged the SunTag system to count membrane-bound myosin motors in actively growing filopodia. Using this approach, we found that the number of myosins is log-normally distributed with a mean of 12.0 ± 2.5 motors [GeoMean ± GeoSD] per filopodium. Together with unitary force values and duty ratio estimates derived from biophysical studies for the motor used in these experiments, we calculate that a distal tip population of myosins could generate a time averaged force of ∼tens of pN to elongate filopodia. This range is comparable to the expected force production of actin polymerization in this system, a point that necessitates revision of popular physical models for protrusion growth.SIGNIFICANCE STATEMENTThis study describes the results of in-cell molecular counting experiments to define the number of myosin motors that are mechanically active in growing filopodia. This data should be used to constrain future physical models of the formation of actin-based protrusions.
Effects of Drought and Salinity,etc.on Root Pressure ofDracaena sanderiana
Authors: Zhang Weizhi , Song Jinfeng , Sang Ying , Zhang Min , Zheng Jiaqi , Liu Yuyang 
Published: May 2024

AbstractAimRoot pressure plays a crucial role in maintaining tissue hydration and ensuring the functionality of the plant’s hydraulic system while facilitating cellular and tissue growth. The study focuses on investigating the impact of drought, salinity,etc.on root pressure ofDracaena sanderiana.MethodsPressure sensors (PX26-100GV) were used to measure the diurnal variations in root pressure of soil-cultured and hydroponicD. sanderianawith heights ranging from 60 to 80 cm. The study also examined various influencing factors such as drought stress, salinity stress, temperatures, mineral concentration, change in leaves and roots that affect root pressure. This approach provides valuable insights into the role of root pressure in mediating water upward movement in xylem.Essential findingsThe research showed: (1) Both soil-cultured and hydroponicD. sanderianaexhibited positive root pressure throughout the day, demonstrating apparent diurnal pattern of high pressures at the day and low pressures at night. The maximum root pressure measured in the experiments was 96 kPa; (2) For soil-culturedD. sanderiana, root pressure decreased under drought and salinization (NaCl), while the diurnal rhythm remained unchanged; (3) For hydroponicD. sanderiana, under simulated drought (PEG 6000) and salt stress (NaCl), the rate of decrease in root pressure accelerated with increasing concentrations of PEG 6000 and NaCl, displaying diurnal rhythm at low concentrations but losing this pattern at high concentrations; (4) Under room temperature, root pressure of hydroponicD. sanderianadecreased with lower water temperature and increased with higher temperatures, but did not increase at 40℃; low concentrations of nitrate (KNO3) generally increased root pressure, however, root pressure decreased when con-centration reached 4 g·L-1, and the diurnal rhythm remained unaffected; (5) For hydroponicD. sanderiana, the presence of leaves on the stem below the root pressure measurement point resulted in significantly lower root pressure compared to plants without leaves on the stem, while still maintaining a regular diurnal rhythm. Removal of all root hairs and the entire root system led to a rapid decline in root pressure to negative values, followed by a slow recovery to around 0 kPa. In conclusion, relative to its height, the root pressure ofD. sanderianais sufficient to transport water required for transpiration to the top of the plant, effectively countering the impact and function of transpirational pull. Moreover, root pressure shows a stable diurnal rhythm of higher values during the day and lower at night. Environmental factors such as drought, salinity stress, temperatures, mineral con-centration, and changes in leaves and roots significantly affect root pressure.