bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of caffeine and brain-related outcomes – a systematic review of observational studies and randomized trials
Authors: Kapellou Angeliki , King Alexandra , Graham Catherine A M , Pilic Leta , Mavrommatis Yiannis 
Published: April 2023

Abstract

Context
Although the stimulant and anxiogenic properties of caffeine are widely accepted, research on its specific effects on the brain remains controversial. Growing evidence shows that interindividual differences in caffeine response may be partly due to variations in genes such as CYP1A2 and ADORA2A, which have been used to identify individuals as “fast” or “slow” caffeine metabolizers and as having a “high” or “low” caffeine sensitivity, respectively.

Objective
The objective of this review was to identify, evaluate, and discuss current evidence on the associations between common genetic variants, caffeine consumption, and brain-related outcomes in humans.

Data Sources
PubMed and Embase databases were searched for relevant reports based on a predetermined search strategy.

Data Extraction
Reports of observational and experimental studies on healthy adults who underwent (a) genetic analysis for polymorphisms in genes associated with caffeine metabolism and effects and (b) measurements of brain-related effects such as anxiety, insomnia, and cognitive performance associated with the consumption of caffeine (habitual intake or supplementation) were included.

Data Analysis
Of the 22 records included, 15 were randomized controlled trials, 6 were cross-sectional studies, and 1 was a genome-wide association study. The main outcomes identified were cognitive performance (n = 9), anxiety (n = 7), and sleep disturbance/insomnia (n = 6). Polymorphisms in the CYP1A2 gene were associated with cognitive function, while variations in the ADORA2A gene were associated with anxiety and sleep disturbance.

Conclusion
The present review has provided evidence that variability in the CYP1A2 and the ADORA2A genes may modulate the association between caffeine and brain-related outcomes. Future studies are warranted to investigate the specific polymorphisms implicated in each brain outcome, which cognitive functions are particularly related to caffeine (simple vs complex), whether there are gender differences in anxiety effects, and how habitual caffeine intake may influence the acute effects of caffeine.

Systematic review registration
PROSPERO registration no. CRD42021257556.
Surgical Margin Affects the Long-Term Prognosis of Patients With Hepatocellular Carcinoma Undergoing Radical Hepatectomy Followed by Adjuvant TACE
Authors: Bai Shilei , Yang Pinghua , Liu Jianwei , Xue Hui , Xia Yong , Liu Fuchen , Yang Zhao , Zhang Lei , Wu Yeye , Shen Feng , Wang Kui 
Published: April 2023

Abstract

Background
The aim of this study was to investigate whether postoperative adjuvant transcatheter arterial chemoembolization (TACE) treatment in wide- and narrow-margin groups could improve the long-term prognosis of patients with hepatocellular carcinoma (HCC).

Materials and Methods
A total of 670 patients with HCC who underwent radical hepatectomy from January 2016 to December 2017 were enrolled, including 397 patients and 273 patients in the wide- and narrow-margin groups. Recurrence-free survival (RFS) and overall survival (OS) outcomes were compared in the wide-margin and narrow-margin groups with and without adjuvant TACE postoperatively, respectively. Propensity score matching (PSM) analysis was used to match patients between TACE and no TACE groups in a 1:1 ratio.

Results
The wide-margin resection was associated with better RFS and OS rates than narrow-margin resection for patients with HCC. Patients with postoperative adjuvant TACE had a better RFS and OS than patients without postoperative adjuvant TACE in the narrow-margin group and reduced the intrahepatic recurrence rate (39.1% vs. 52.6%, P = .036) and the local recurrence rate in the liver (11.2% vs. 21.4%, P = .032). But postoperative adjuvant TACE did not alter recurrence and survival outcomes in the wide-margin group. Similar results were noted after propensity score matching (PSM).

Conclusion
The wide-margin resection had better RFS and OS than the narrow-margin resection for patients with HCC. Postoperative adjuvant TACE was associated with reduced recurrence and improved OS after narrow-margin resection, but was not effective in the wide-margin resection.
Experiences of Mothers of Preterm Infants in the Neonatal Intensive Care Unit During the COVID-19 Pandemic
Authors: Richter Lindsay L. , Ku Connie , Mak Meagan Yan Yu , Holsti Liisa , Kieran Emily , Alonso-Prieto Esther , Ranger Manon 
Published: April 2023

Background:
The neonatal intensive care unit (NICU) stay following the birth of a preterm infant can be stressful and traumatic for families. During the COVID-19 pandemic, the NICU environment changed precipitously as infection control and visitor restriction measures were implemented.

Purpose:
Our study aimed to examine the impact of the pandemic policies on the experiences of mothers of preterm infants during their stay in the NICU.

Methods:
Semistructured interviews were conducted with mothers of preterm infants hospitalized in a Canadian tertiary-level NICU. Informed by interpretive description methodology, interview content was transcribed and analyzed using a thematic analysis approach. The identified themes were validated, clarified, or refined using investigator triangulation.

Results:
Nine English-speaking mothers, aged 28 to 40 years, were interviewed. Four themes emerged from the analysis of their experiences: (1) disrupted family dynamic, support, and bonding; (2) physical and emotional isolation; (3) negative psychological impact compounded by added concerns, maternal role change, and survival mode mentality; and (4) positive aspects of the pandemic management measures.

Implications for Practice:
During the pandemic, the way that care was provided in the NICU changed. This study helps to explore how neonatal clinicians can foster individual and organizational resilience to keep patients and families at the center of care, even when the healthcare system is under intense stress.

Implications for Research
: Our results show that these changes heightened mothers' distress, but also had a modest positive impact. Further research about long-term consequences of pandemic policies on the mother and preterm infant after NICU discharge is warranted.
Parental Perceptions of the Impact of NICU Visitation Policies and Restrictions Due to the COVID-19 Pandemic
Authors: Yance Brittany , Do Kayla , Heath Jenna , Fucile Sandra 
Published: April 2023

Background:
The COVID-19 pandemic has impacted parents' ability to participate in their infants' care during the neonatal intensive care unit (NICU) stay in unprecedented ways.

Purpose:
The purpose of this study was to explore the lived experience of parents whose infants was in the NICU during the COVID-19 pandemic.

Methods:
A qualitative telephone interview survey was conducted. Participants included parents of preterm infants who were born less than 34 weeks' gestation during the first wave of the COVID-19 pandemic (March 2020-August 2020). Telephone surveys were conducted through open-ended questions. A thematic content analysis identifying themes was performed after interviews were completed and transcribed.

Results:
A total of 8 mothers completed the telephone survey. Key themes from this study include parents experiencing increased stress due to the restricted visitation policies, limited opportunities to care for their infant, lack of support, and inconsistent communication regarding their infant status and COVID-19 protocols.

Implications for Practice:
Suggestions provided to enhance NICU services during the pandemic include increasing parental engagement opportunities to care for their infant in the NICU, enhanced empathy and compassion from the neonatal team, and open and transparent communication.

Implications for Research:
Further research investigating cultural impact on parents' perspectives, perspectives of fathers, long-term impact of how parents coped after discharge from the NICU, and emotional impact on NICU staff members may be beneficial to aid improvements in NICU service delivery during the ongoing and future pandemic.
MicroRNA-322 inhibition of calcification of arterial smooth muscle cells by regulation of galactosyltransferase 1-associating protein UBE2Q1 and Runx2
Authors: Gao Shanshan , Gao Song , Sun Zhen , Akesson Mikael , Shelat Harnath S. , Geng Yongjian 
Published: April 2023

Background and purpose:
Vascular smooth muscle cell (SMC) calcification represents a prominent phenotypic alteration in atherosclerosis. MicroRNA-322 (miR-322) is crucially involved in myogenic stem cell growth and differentiation. The galactosyltransferase 1-associated protein (GTAP) is a ubiquitin-conjugating enzyme E2Q1 (UBE2Q1) that serves as a critical mediator of post-translational regulation of certain cellular enzymes and transcription factors. Runt-related transcription factor 2 (Runx2) plays a critical role in arterial calcification. However, the interplay between miR-322, UBE2Q1, and Runx2 during cardiovascular calcification remain largely unknown. Therefore, the purpose of this study is to delineate the molecular mechanisms by which miR-322 regulates vascular calcification.

Methods:
Here we examined miR-322 expression in murine SMC, and determined whether miR-322 regulates SMC calcification via modulating expression of UBE2Q1 and calcifying proteins. Murine SMC cultures or aortic segments were exposed to inorganic phosphate (Pi) for induction of calcification. Expressions of calcification-related genes in SMC with lentivirus-mediated knockdown of UBE2Q1 were determined with Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Luciferase reporter assay was performed to validate miR-322 target binding and SMC were transfected with anti-miR-322 oligonucleotides to inhibit miR-322 function.

Results:
Aortic rings derived from UBE2Q1−/− mice exhibited much higher calcium content compared to aortic rings from wildtype (WT) animals, following calcification induction. Knockdown of UBE2Q1 by lentiviral short hairpin RNA (shRNA) significantly enhanced the calcium deposition and expression of osteogenic gene Runx2 in SMC. Enhanced UBE2Q1 expression dramatically reduced calcification while promoting expression of contractile proteins SM22α and α-SMA. Treatment with anti-miR-322 diminished the luciferase activity in SMC transfected with the reporter gene driven by the 3′-untranslated region of UBE2Q1 mRNA. Anti-miR-322 treatment also inhibited calcification significantly.

Conclusions:
Our study identified miR-322 regulates vascular calcification by targeting UBE2Q1. The miR-322–dependent regulation of UBE2Q1 and calcification represents a novel regulatory mechanism that controls vascular SMC function during the pathogenesis of vascular calcification.
A Case of Penile Herpes Zoster
Authors: Aflatooni S. , Ahadiat O. 
Published: April 2023

Introduction:
Herpes zoster (HZ) manifests as vesicular lesions typically involving thoracic dermatomes and rarely sacral dermatomes.
Here, we present the case of a 32-year-old immunocompetent man with an atypical presentation of HZ misdiagnosed as herpes simplex virus (HSV).

Case presentation:
A 32-year-old man first presented with an erythematous rash with increasing pain severity on the right side of the glans penis involving the S2–S3 dermatomes. Repeated polymerase chain reaction (PCR) tests yielded negative results for both HZ and HSV. The appearance of vesicular lesions on the penis led to an initial misdiagnosis of HSV, causing a great emotional burden on the patient.

Discussion:
HZ occurs uncommonly in the sacral dermatomes. The clinical manifestations of HSV and HZ are similar and must be distinguished via careful diagnostic approaches using PCR testing. The unique symptoms of HZ are unilateral vesicular lesions and post-herpetic neuralgia.

Conclusion:
Penile HZ should be considered in patients presenting with unilateral, localized vesicular lesions.
Most Frequent Comorbidities in Patients with Lichen Planopilaris: A Cross-Sectional Study
Authors: Gharaei Nejad Kaveh , Ghadarjani Reyhaneh , Eftekhari Hojat , Sheykholeslami Saba 
Published: April 2023

Background:
Lichen planopilaris (LPP) is a rare skin disorder, but it is also the most common cause of scarring alopecia in adults. The main cause of this disease is unknown, but it is considered to be related to the immune status of the body. Several comorbidities are reportedly associated with LPP, such as hypertension, depression, thyroiditis, diabetes, and vitiligo.

Objective:
In the present study, we aimed to investigate the frequency of comorbidities in patients with LPP who were referred to Razi Hospital in Rasht, Iran from 2016 to 2019.

Methods:
This cross-sectional study involved 60 patients with cicatricial alopecia patches (scarring and irreversible) and clinical signs and symptoms consistent with active LPP. The patients’ demographic data and clinical characteristics were recorded and analyzed using SPSS Version 21, and the level of statistical significance was set at 0.05.

Results:
The results showed that the most common comorbidities were vitamin D deficiency (24.3%), hypothyroidism (17.6%), anemia (16.2%), asthma and allergy (14.8%), hypertension (13.5%), diabetes (9.5%), and vitiligo (4.5%). There was no statistically significant association of sex, age, or body mass index with LPP according to the presence or absence of underlying disease (P = 0.44, P = 0.108, and P = 0.34, respectively); however, there was a statistically significant difference in the presence of comorbidities according to age (P = 0.018).

Conclusion:
The results illustrated that women with vitamin D deficiency are more prone to LPP than are patients with other pre-existing underlying diseases.
Long-term Survival, Quality of Life, and Molecular Features of the Patients With Solid Pseudopapillary Neoplasm of the Pancreas
Authors: Liu Qiaofei , Dai Menghua , Guo Junchao , Wu Huanwen , Wang Weibin , Chen Ge , Hu Ya , Han Xianlin , Xu Qiang , Zhang Xiang , Yang Sen , Zhang Yalu , Kleeff Jorg , Liao Quan , Wu Wenming , Liang Zhiyong , Zhang Taiping , Zhao Yupei 
Published: April 2023

Objective:
To present comprehensive information on the clinicopathological, molecular, survival characteristics, and quality of life (QOL) after surgery for solid pseudopapillary neoplasm (SPN) of the pancreas in a large cohort after long-term follow-up.

Background:
SPN is a rare tumor with an uncertain malignant potential, and solid information on long-term prognosis and QOL remains limited.

Methods:
All hospitalized patients with SPNs who underwent surgery between 2001 and 2021 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinicopathological characteristics of the patients were retrieved. A cross-sectional telephone questionnaire was administered to inquire about the QOL. Molecular analyses were performed using whole-exome sequencing.

Results:
Exactly 454 patients with SPN were enrolled, of whom 18.5% were males and 81.5% were females. The mean patient age was 31 ± 12 years. In total, 61.3% of the patients had no symptoms. The size of the tumors was 5.38 ± 3.70 cm; 83.4% were solid cystic tumors, and 40.1% had calcifications. The proportions of local resection, distal pancreatectomy with or without splenectomy, and pancreaticoduodenectomy with or without pylorus preservation were 29.7%, 28.9% or 22.9%, and 11% or 6.8%, respectively. Over the years, there has been a significant shift from open to minimally invasive surgery. Among all surgical procedures, pylorus-preserving pancreaticoduodenectomy (PPPD) had the highest incidence of grade 2 to 4 complications (up to 32.3%), compared with 6.7% in distal pancreatectomy (P < 0.001). Regarding histopathology, tissue invasion, perineural invasion, cancerous microvascular emboli, lymph node metastasis, and distant metastasis were present in 16.5%, 2.2%, 0.7%, 2.0%, and 3.1% of patients, respectively. Sixty patients were lost to follow-up. Sixteen of the 390 patients who underwent resection (4.1%) experienced local recurrence or distant metastasis after surgery. In total, 361 patients responded to the telephone survey. Nearly 80% of patients claimed their QOL was not significantly affected after surgery; however, the remaining 20% complained of lower QOL during 3 to 6 years of follow-up after surgery. No clinicopathological factor could reliably predict clinical recurrence or metastasis after resection. A total of 28 driver genes were detected with mutations in at least 2 tumor samples and the top 3 frequently mutated genes were CTNNB1, ATRNL1, and MUC16.

Conclusions:
This study presented the largest cohort of patients with SPN after surgery from a single center and reported the QOL of these patients. SPN is associated with extremely favorable long-term survival, even in patients with metastasis, and most patients have a good QOL after surgery.
Mechanistic basis for oxidative stress protection of the human tRNA ligase complex by the oxidoreductase PYROXD1
Authors: Loeff Luuk , Kroupova Alena , Asanović Igor , Boneberg Franziska , Pfleiderer Moritz , Ferdigg Andrè , Ackle Fabian , Martinez Javier , Jinek Martin 
Published: April 2023

AbstractRTCB is the catalytic subunit of the metazoan tRNA ligase complex (tRNA-LC) that plays essential roles in tRNA biogenesis and unfolded protein response. The catalytic center of RTCB contains a conserved cysteine that is susceptible to metal ion-induced oxidative inactivation. The flavin-containing oxidoreductase PYROXD1 preserves the activity of mammalian tRNA-LC in a NAD(P)H-dependent manner, but its protective mechanism remains elusive. Here we report a cryo-EM structure of human RTCB in complex with PYROXD1, revealing that PYROXD1 directly interacts with the catalytic center of RTCB through its C-terminal tail. NAD(P)H binding and FAD reduction allosterically control PYROXD1 activity and RTCB recruitment and PYROXD1, while PYROXD1 reoxidation enables timed release of RTCB. PYROXD1 interaction is mutually exclusive with Archease-mediated RTCB guanylylation, and guanylylated RTCB is intrinsically protected from oxidative inactivation. Together, these findings provide a mechanistic framework for the protective function of PYROXD1 that maintains the activity of tRNA-LC under aerobic conditions.
Systematic visualisation of molecular QTLs reveals variant mechanisms at GWAS loci
Authors: Kerimov Nurlan , Tambets Ralf , Hayhurst James D. , Rahu Ida , Kolberg Peep , Raudvere Uku , Kuzmin Ivan , Chowdhary Anshika , Vija Andreas , Teras Hans J. , Kanai Masahiro , Ulirsch Jacob , Ryten Mina , Hardy John , Guelfi Sebastian , Trabzuni Daniah , Kim-Hellmuth Sarah , Rayner Will , Finucane Hilary , Peterson Hedi , Mosaku Abayomi , Parkinson Helen , Alasoo Kaur 
Published: April 2023

AbstractSplicing quantitative trait loci (QTLs) have been implicated as a common mechanism underlying complex trait associations. However, utilising splicing QTLs in target discovery and prioritisation has been challenging due to extensive data normalisation which often renders the direction of the genetic effect as well as its magnitude difficult to interpret. This is further complicated by the fact that strong expression QTLs often manifest as weak splicing QTLs and vice versa, making it difficult to uniquely identify the underlying molecular mechanism at each locus. We find that these ambiguities can be mitigated by visualising the association between the genotype and average RNA sequencing read coverage in the region. Here, we generate these QTL coverage plots for 1.7 million molecular QTL associations in the eQTL Catalogue identified with five quantification methods. We illustrate the utility of these QTL coverage plots by performing colocalisation between vitamin D levels in the UK Biobank and all molecular QTLs in the eQTL Catalogue. We find that while visually confirmed splicing QTLs explain just 6/53 of the colocalising signals, they are significantly less pleiotropic than eQTLs and identify a prioritised causal gene in 4/6 cases. All our association summary statistics and QTL coverage plots are freely available athttps://www.ebi.ac.uk/eqtl/.
Frugivory and seed predation of fishtail palm (Caryota mitisLour.) on the remote oceanic island of Narcondam, India
Authors: Gopal Abhishek , Ghuman Sartaj , Ramachandran Vivek , Page Navendu , Naniwadekar Rohit 
Published: April 2023

ABSTRACTOceanic islands, due to their evolutionary history and isolation, hold a disproportionately high proportion of endemic species. However, their evolutionary history also makes them vulnerable to extinctions, with most known extinctions occurring on islands. Plant-animal interactions are particularly important on islands, as island systems generally have low redundancy and are more vulnerable to disruption either via extinction or by invasive species. Here, we examined the fruit removal and seed predation of a keystone palm,Caryota mitis, on the remote oceanic island of Narcondam. The island endemic Narcondam hornbill (Rhyticeros narcondami), was the sole seed disperser of theCaryota mitis(90 hours; N = 15 trees), indicating a lack of redundancy in seed dispersal of the palm on this island. While the invasive rodent,Rattuscf.tiomanicuswas the sole predator of theCaryota mitisseeds in the forest (N = 15 individual fruiting palms, 416 trap nights). Overall, 17.1% of the seeds placed (N = 375 seeds) were removed. Seeds placed under and away from the canopy, and at different densities (2 plots with 10 seeds each; 1 plot with 5 seeds, respectively), showed similar removal rates. This is indicative of ambient seed predation and the lack of safe sites for the regeneration ofCaryota mitis, with potential deleterious effects on the subsequent stages of the “seed dispersal cycle”. Here, from a data deficient site, we provide baseline information on the plant-frugivore interaction of a keystone palm and the potential impacts by an invasive rodent.
Detailed Social Network Interactions and Gut Microbiome Strain-Sharing Within Isolated Honduras Villages
Authors: Pullman Jackson , Beghini Francesco , Alexander Marcus , Shridhar Shivkumar Vishnempet , Prinster Drew , Brito Ilana L. , Christakis Nicholas A. 
Published: April 2023

AbstractWhen humans assemble into face-to-face social networks, they create an extended environment that permits exposure to the microbiome of other members of a population. Social network interactions may thereby also shape the composition and diversity of the microbiome at individual and population levels. Here, we use comprehensive social network and detailed microbiome sequencing data in 1,098 adults across 9 isolated villages in Honduras to investigate the relationship between social network structure and microbiome composition. Using both species-level and strain-level data, we show that microbial sharing occurs between many relationship types, notably including non-familial and non-household connections. Using strain-sharing data alone, we can confidently predict a wide variety of relationship types (AUC ~0.73). This strain-level sharing extends to second-degree social connections in a network, suggesting the importance of the extended network with respect to microbiome composition. We also observe that socially central individuals are more microbially similar to the overall village than those on the social periphery. Finally, we observe that clusters of microbiome species and strains occur within clusters of people in the village social networks, providing the social niches in which microbiome biology and phenotypic impact are manifested.