bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment
Authors: Pulvirenti Alessandra , Javed Ammar A. , Michelakos Theodoros , Sekigami Yurie , Zheng Jian , Kalvin Hannah L. , McIntyre Caitlin A. , Nebbia Martina , Chou Joanne F. , Gonen Mithat , Raj Nitya , Reidy-Lagunes Diane L. , Zureikat Amer H. , Ferrone Cristina R. , He Jin , Wei Alice C. ,   PAncreatic Neuroendocrine Disease Alliance (PANDA)
Published: January 2023

Objective:
The objective of this study was to describe the pattern of recurrence, treatments received, as well the oncological outcomes, of pancreatic neuroendocrine tumors (PanNETs) following curative surgery.

Background:
PanNETs recur in 10% to 15% of cases following surgery. Information on the natural history and management of recurring disease is lacking.

Materials and Methods:
Patients with PanNET that underwent curative surgery at 4 institutions between 2000 and 2019 were identified. Patients with poorly differentiated tumors, unknown tumor grade and differentiation, hereditary syndromes, unknown margin or R2 status, metastatic, and those that had neoadjuvant treatment or perioperative mortality were excluded. Clinical variables were assessed including first site of recurrence, treatment received, and survival outcomes.

Results:
A total of 1402 patients were included: 957 (74%) had grade 1, 322 (25%) had grade 2, and 13 (1%) had grade 3 tumors. Median follow-up was 4.8 years (interquartile range: 2–8.2 years). Cumulative incidence of recurrence at 5 years was 13% (95% CI: 11%–15.2%) for distant disease, 1.4% (95% CI: 0.8%–2.3%) for locoregional recurrence, and 0.8% (95% CI: 0.4%–1.5%) for abdominal nodal recurrence. Patients who recurred had 2.89 increased risk of death (95% CI: 2–4.1) as compared with patients who did not recur. Therapy postrecurrence included: somatostatin analogs in 111 (61.0%), targeted therapies in 48 (26.4%), liver-directed therapies in 61 (33.5%), peptide receptor radionuclide therapy in 30 (16.5%), and surgery in 46 (25.3%) patients. Multiple treatments were used in 103 (57%) cases. After the first recurrence, 5-year overall survival was 74.6% (95% CI: 67.4%–82.5%).

Conclusions:
Recurrence following surgery is infrequent but reduces survival. Most recurrences are distant and managed with multiple therapies. Prospective studies are needed to establish strategies for surveillance and the sequence of treatment to control the disease and prolong survival.
Modern Outcomes After Liver Retransplantation: A Single-center Experience
Authors: Connor Ashton A. , Saharia Ashish , Mobley Constance M. , Hobeika Mark J. , Victor David W. , Kodali Sudha , Brombosz Elizabeth W. , Graviss Edward A. , Nguyen Duc T. , Moore Linda W. , Gaber A. Osama , Ghobrial R. Mark 
Published: January 2023

Background.
The need for liver retransplantation (reLT) has increased proportionally with greater numbers of liver transplants (LTs) performed, use of marginal donors, degree of recipient preoperative liver dysfunction, and longer survival after LT. However, outcomes following reLT have been historically regarded as poor.

Methods.
To evaluate reLT in modern recipients, we retrospectively examined our single-center experience. Analysis included 1268 patients undergoing single LT and 68 patients undergoing reLT from January 2008 to December 2021.

Results.
Pre-LT mechanical ventilation, body mass index at LT, donor–recipient ABO incompatibility, early acute rejection, and length of hospitalization were associated with increased risk of needing reLT following index transplant. Overall and graft survival outcomes in the reLT cohort were equivalent to those after single LT. Mortality after reLT was associated with Kidney Donor Profile Index, national organ sharing at reLT, and LT donor death by anoxia and blood urea nitrogen levels. Survival after reLT was independent of the interval between initial LT and reLT, intraoperative packed red blood cell use, cold ischemia time, and preoperative mechanical ventilation, all previously linked to worse outcomes.

Conclusions.
These data suggest that reLT is currently a safer option for patients with liver graft failure, with comparable outcomes to primary LT.
Temporary Mechanical Circulatory Support Use and Clinical Outcomes of Simultaneous Heart/Kidney Transplant Recipients in the Pre– and Post–heart Allocation Policy Change Eras
Authors: Agdamag Arianne C. , Riad Samy , Maharaj Valmiki , Jackson Scott , Fraser Meg , Charpentier Victoria , Nzemenoh Bellony , Martin Cindy M. , Alexy Tamas 
Published: January 2023

Background.
The use of temporary mechanical circulatory support (tMCS) devices (intra-aortic balloon pump; Impella 2.5, CP, 5.0; venoarterial extracorporeal membrane oxygenation) increased significantly across the United States for heart transplant candidates after the allocation policy change. Whether this practice change also affected simultaneous heart-kidney (SHK) candidates and recipient survival is understudied.

Methods.
We used the Scientific Registry of Transplant Recipients database to identify adult SHK recipients between January 2010 and March 2022. The population was stratified into pre– and post–heart allocation change cohorts. Kaplan–Meier curves were generated to compare 1-y survival rates. A Cox proportional hazards model was used to investigate the effect of allocation period on patient survival. Recipient outcomes bridged with eligible tMCS devices were compared in the post–heart allocation era. In a separate analysis, SHK waitlist mortality was evaluated between the allocation eras.

Results.
A total of 1548 SHK recipients were identified, and 1102 were included in the final cohort (534 pre-allocation and 568 post-allocation change). tMCS utilization increased from 17.9% to 51.6% after the allocation change, with venoarterial extracorporeal membrane oxygenation use rising most significantly. However, 1-y post-SHK survival remained unchanged in the full cohort (log-rank P = 0.154) and those supported with any of the eligible tMCS devices. In a separate analysis (using a larger cohort of all SHK listings), SHK waitlist mortality at 1 y was significantly lower in the current allocation era (P  = 0.002).

Conclusions.
Despite the remarkable increase in tMCS use in SHK candidates after the heart allocation change, 1 y posttransplant survival remained unchanged. Further studies with larger cohorts and longer follow-ups are needed to confirm these findings.
Exosomes for the diagnosis and treatment of dementia
Authors: Joo Hyeon Su , Jeon Ha Yeong , Hong Eun Be , Kim Ha Young , Lee Jung Min 
Published: January 2023

Purpose of review
Dementia is a syndrome with several possible pathologies. To date, definitive methods for diagnosis and treatment of sub-types of dementia have not been established. Emerging evidence suggests that exosomes can provide important information for the diagnosis and treatment of several subtypes of dementia. This article reviews recent studies on the application of exosomes in dementia.

Recent findings
Exosomes are involved in the pathogenesis of Alzheimer's disease (AD) and Parkinson's disease (PD) through transporting toxic proteins such as amyloid beta (Aβ), tau, and α-synuclein. Exosomal microRNAs (miR) and proteins reflect the disease state, and therefore, exosomes can be used as diagnostic markers for diseases such as AD, PD, Huntington's disease (HD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Mesenchymal stem cell (MSC)-derived exosomes have been shown to ameliorate disease pathology, and improve cognitive function in AD, PD, and VAD.

Summary
Recent studies have shown that exosomes could be novel diagnostic agents for dementia because they contain molecules that could be potential biomarker candidates indicative of the type and stage of dementia. Therapeutic application of exosomes in dementia has revealed that exosomes only, or exosomes loaded with an active pharmaceutical ingredient (API), ameliorate disease phenotype of dementia. Further work is needed to exploit this potential.
Further development needed: models of post-diagnostic support for people with dementia
Authors: Low Lee-Fay , Gresham Meredith , Phillipson Lyn 
Published: January 2023

Purpose of review
There is increasing recognition of a service gap immediately after diagnosis for people with dementia and carers. This narrative review of models of post-diagnostic support focuses on recent developments and offers suggestions for future development. We present the current evidence for these models and consider the service components they provide against the recommendations of clinical guidelines and principles underpinning ideal post-diagnostic support.

Recent findings
Models of post-diagnostic support include a short-term support worker, ongoing support worker, centre-based support, primary care management, and specialist dementia clinics. Of these, specialist dementia clinics that include ongoing support workers provide most components of an ideal and timely post-diagnostic support framework, but may be more costly to implement universally. The greatest research evidence is for the benefits of long-term support models, specifically case management, though this does not necessarily include medical care or nonpharmacological interventions. There is sparce evidence for the benefits of short-term support worker models such as dementia advisers for people with dementia and carers.

Summary
Further development is needed to create whole-system models of dementia support which meet the needs of people with dementia and their carers, are timely, accessible and equitable, and can be implemented universally.
Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlightsAPOL1as a high risk locus in patients with diabetic macular edema
Authors: Stockwell Amy D. , Chang Michael C. , Mahajan Anubha , Forrest William , Anegondi Neha , Pendergrass RK , Selvaraj Suresh , Reeder Jens , Wei Eric , Iglesias VA , Creps Natalie M. , Macri Laura , Neeranjan Andrea N. , van der Brug Marcel P. , Scales Suzie J. , McCarthy Mark I. , Yaspan Brian L. 
Published: January 2023

AbstractDiabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5×10−8). The strongest association was rs2239785, (K150E) inAPOL1. The second finding was rs10402468, which co-localized toPLVAPandANKLE1in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the geneAPOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries.
Breastfeeding support for mothers of low birth weight infants using mother-to-mother peers in rural western Kenya - a feasibility study
Authors: Dickinson Fiona M , Achieng Florence , K’Oloo Alloys , Otiti Iwaret , Tindi Linda , Boga Mwanamvua , Kimani Mary , Kiige Laura , Mellor Kathy , Dellicour Stephanie , Barsosio Hellen C. , Kariuki Simon , Nabwera Helen M 
Published: January 2023

AbstractThe majority of the 2.4 million neonates (infants<28 days) who died in 2020 were born weighing <2500g i.e. low birth weight (LBW). In Africa, approximately 1 in 10 neonates are LBW. The majority of those who survive beyond the neonatal period are undernourished, have neuro-developmental impairment, or die before their second birthday. Unaddressed feeding difficulties contribute significantly to these adverse outcomes. This study assessed the feasibility and acceptability of using trained mother-to-mother peers (peer-mothers) to deliver breastfeeding support to mothers of LBW infants in healthcare facilities in rural Kenya.A mixed methods approach was employed, using structured observations, and pre- and post-intervention semi-structured interviews, with mothers, healthcare providers and peer-mothers. Six trained peer-mothers delivered the interventions to the mother-LBW infant pairs across eight healthcare facilities in Homa Bay County. Descriptive statistics were used to analyse the quantitative data and thematic analysis for the qualitative data.From September-November 2021, 23 mothers and 26 LBW infants were recruited and received the intervention. All infants were born in a hospital, the median age of the infants was 1 day (Interquartile range, IQR 1,3), birth weight 2100g (IQR 1900, 2260) and recorded gestation 34 weeks (IQR 34,36). Although all mothers looked well, 4 (17%) showed no signs of bonding with their infant. One infant was too weak to suckle and was referred to healthcare providers. Key themes were challenges with infant feeding decision-making among mothers of LBW infants, community misconceptions of recommended infant feeding practices for LBW infants, and the integral role of peer-mothers in maternity units.Facility-based, breastfeeding peer support for LBW infants was feasible and acceptable in the context of resource constraints. It could improve uptake of appropriate infant feeding practices among these vulnerable infants and enhance their post-discharge survival and growth outcomes. This strategy warrants further evaluation in a larger study.
Effectiveness of Ferritin-guided Donation Intervals in Blood Donors: Results of the Stepped-wedge Cluster Randomised FIND’EM Trial
Authors: Meulenbeld Amber , Ramondt Steven , Sweegers Maike G. , Quee Franke A. , Prinsze Femmeke J. , Hoogendijk Emiel O. , Swinkels Dorine W. , van den Hurk Katja 
Published: January 2023

AbstractBackgroundWhole blood donors are at increased risk for iron deficiency and anaemia. The current standard of haemoglobin (Hb) monitoring is insufficient to ensure the maintenance of proper iron reserves and donor health. We determine the effects of ferritin-guided donation intervals for blood donors and the blood supply.MethodsA ferritin-guided donation interval policy was implemented and evaluated through a stepped-wedge cluster-randomised controlled trial in all blood collection centres in the Netherlands. Ferritin was measured in new donors and at every 5th donation. Subsequent donation intervals were extended to six months if ferritin was 15 - 30 ng/mL and to twelve months if ferritin was <15 ng/mL. Primary outcomes are ferritin and Hb levels, iron deficiency, Hb deferral, and donor return. Secondary outcomes are self-reported iron deficiency-related symptoms. Operational statistics assessed the impact on the blood supply.FindingsAmong 412,888 whole blood donors, 36,099 were measured. Ferritin-guided intervals increased ferritin levels by 0.24 log10 ng/mL (95% CI 0.22 – 0.27, p <0.001) and Hb by 0.37 g/dL (95% CI 0.31 –0.43, p <0.001). Donors were less likely to be iron deficient (OR 0.15, 95% CI 0.10 – 0.21, p <0.001) or deferred based on Hb (OR 0.23, 95% CI 0.11 – 0.41, p <0.001). However, donors returned less frequently (OR 0.60, 95% CI 0.51 – 0.67, p <0.001), necessitating more invitations and reducing the average donation frequency. No improvement in self-reported symptoms was observed.InterpretationFerritin-guided donation intervals significantly improved Hb and ferritin levels, reducing iron deficiency and Hb deferrals. While beneficial for iron and Hb maintenance, efforts are needed to recruit and retain donors and remedy self-reported symptoms.Funding and registrationThis project received support from the ’Product and Process Development Cellular Products Grant’ (PPOC18-15) granted to K. van den Hurk by the Research Programming Committee of Sanquin. The trial was registered in the Dutch trial registry (NTR6738) on September 29th, 2017 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6738).
Atypical cognitive training-induced learning and brain plasticity and their relation to insistence on sameness in children with autism
Authors: Liu Jin , Chang Hyesang , Abrams Daniel A. , Kang Julia Boram , Chen Lang , Rosenberg-Lee Miriam , Menon Vinod 
Published: January 2023

AbstractChildren with autism spectrum disorders (ASD) often display atypical learning styles, however little is known regarding learning-related brain plasticity and its relation to clinical phenotypic features. Here, we investigate cognitive learning and neural plasticity using functional brain imaging and a novel numerical problem-solving training protocol. Children with ASD showed comparable learning relative to typically developing children but were less likely to shift from rule-based to memory-based strategy. Critically, while learning gains in typically developing children were associated with greater plasticity of neural representations in the medial temporal lobe and intraparietal sulcus, learning in children with ASD was associated with more stable neural representations. Crucially, the relation between learning and plasticity of neural representations was moderated by insistence on sameness, a core phenotypic feature of ASD. Our study uncovers atypical cognitive and neural mechanisms underlying learning in children with ASD, and informs pedagogical strategies for nurturing cognitive abilities in childhood autism.
HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways
Authors: Monda Julie K , Ge Xuezhen , Hunkeler Moritz , Donovan Katherine A , Ma Michelle W , Jin Cyrus Y , Leonard Marilyn , Fischer Eric S , Bennett Eric J 
Published: January 2023

SummaryHUWE1 is a large, enigmatic HECT domain ubiquitin ligase implicated in the regulation of diverse pathways including DNA repair, apoptosis, and differentiation. How HUWE1 engages its structurally diverse substrates and how HUWE1 activity is regulated are unknown. Using unbiased quantitative proteomics, we identify C16orf72/HAPSTR1 as a dedicated HUWE1 substrate despite HUWE1 targeting substrates in a largely cell type-specific manner. The established physical and genetic interactions between HUWE1 and C16orf72/HAPSTR1 suggest that HAPSTR1 positively regulates HUWE1 function. Here, we show that HAPSTR1 is both a HUWE1 substrate and is required for HUWE1 nuclear localization to facilitate HUWE1 nuclear substrate targeting. HUWE1 or HAPSTR1 loss of function triggers a broad transcriptional stress response. We show that nuclear HUWE1 is both critical for modulating stress signaling pathways, which include p53 and NF-κB-mediated signaling and required for cell proliferation. Combined, our results define a role for HAPSTR1 in gating critical nuclear HUWE1 functions.
The Glucocorticoid Receptor is Required for Efficient Aldosterone-Induced Transcription by the Mineralocorticoid Receptor
Authors: Johnson Thomas A. , Fettweis Gregory , Wagh Kaustubh , Almeida-Prieto Brian , Krishnamurthy Manan , Upadhyaya Arpita , Hager Gordon L. , Alvarez de la Rosa Diego 
Published: January 2023

ABSTRACTThe glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have distinct, yet overlapping physiological and pathophysiological functions. There are indications that both receptors interact functionally and physically, but the precise role of this interdependence is poorly understood. Here, we analyzed the impact of GR co-expression on MR genome-wide chromatin binding and transcriptional responses to aldosterone and glucocorticoids, both physiological ligands of this receptor. Our data show that GR co-expression alters MR genome-wide binding to consensus DNA sequences in a locus-and ligand-specific way. MR binding to consensus DNA sequences is affected by GR. Transcriptional responses of MR in the absence of GR are weak and show poor correlation with chromatin binding. In contrast, co-expression of GR potentiates MR-mediated transcription, particularly in response to aldosterone. Finally, single-molecule tracking of MR suggests that the presence of GR contributes to productive binding of MR/aldosterone complexes to chromatin. Together, our data indicate that co-expression of GR potentiates aldosterone-mediated MR transcriptional activity, even in the absence of glucocorticoids.
An evaluation of the effectiveness of a therapeutic program for children with global developmental delay
Authors: Al-Yamani Abyan Ismail , Sulaiman Nabil Ali , Al-Ansari Ahmed Malalla 
Published: January 2023

PurposeGlobal developmental delay (GDD) is highly prevalent among patients at child psychiatry clinics. However, preschool day treatment centers are currently scarce. As such, this study aimed to evaluate a program that was designed for children with GDD in order to improve their global skills and prepare them to join the school system.Design/methodology/approachThis study utilized an observation retrospective design with a comparative group sample and included all children aged between 3 and 6 years who participated in the program for at least one academic year (experimental group). Their GDD diagnoses were based on the DSM-5 criteria (Diagnostic and Statistical Manual of Mental Disorders). Children with similar diagnoses who were on the waiting list constituted the control group. Pre- and post-scoring of the Children’s Global Assessment Scale (CGAS) were conducted by the children’s teacher and blinded investigator for the experimental group, while the children’s mothers conducted the post-CGAS scoring for the control group.FindingsThe pre- and post-CGAS scores for the experimental group were 49.5 ± 12.8 and 58.3 ± 12.7 and 47.3 ± 17.3 and 66.6 ± 17.3 for the control group, respectively (p = 0.001). The children in the experimental group scored significantly better than the control group with respect to securing places in integrated, regular classes in the education system (p = 0.001).Research limitations/implicationsThis study had certain limitations. First, the number of children in the control group was relatively small. Second, the baseline skill levels of some of the children in the control group may have been lower than those of the children in the experimental group at the beginning of the evaluation; this may explain why they had been put on the waiting list. Third, the information was gathered retrospectively; this is a method that is known to have its own limitations.Practical implicationsThe clinical implications of the study are that the early identification and referral of GDD are key elements in the rehabilitation of these children and that early intervention programs are necessary for cases of moderate and severe GDD. Primary care physicians should follow up with GDD patients to ensure that referrals are being appropriately sought (Choo et al., 2019).Originality/valueThe program was effective in both increasing the general functioning skills of the children in the experimental group and preparing them to attend regular, integrated classes. The program should be expanded and made available to more children with GDD.