bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life in outpatients with substance use disorder: evolution over time and associated factors
Authors: Simirea Melexima , Baumann Cédric , Bisch Michael , Rousseau Hélène , Di Patrizio Paolo , Viennet Sarah , Bourion-Bédès Stéphanie 
Published: February 2022

Abstract
Background
Health-related quality of life (HRQoL) is an important element of patient care and clinical research. The aim of this study was to describe HRQoL changes and identify associated factors during a 6-month follow-up of outpatients starting care for alcohol or opioid dependence.

Methods
HRQoL was measured at baseline and 3 and 6 months later using the SF-12. Data on the patients’ sociodemographics, clinical characteristics and levels of anxiety and depression were collected using the Hospital Anxiety and Depression Scale (HADS). Repeated-measures analyses were performed to assess factors associated with global HRQoL differences and the evolution of HRQoL indicated by both physical and mental scores (PCS and MCS, respectively).

Results
The mean PCS and MCS scores were initially low at 45.4 (SD = 8.6) and 36.0 (SD = 10.9), respectively. The improvement in HRQoL was rapid in the first 3-month period and then slowed and remained stable over the subsequent 3-month period. Being employed (p = 0.012), having no comorbidities (p = 0.014) and having no depression (p = 0.004) were associated with significant differences in the average PCS scores at the 3 time points. Patients who had lower overall HRQoL MCS scores on average were those for whom a medication was initiated (p = 0.009), as was the case for patients with anxiety (p < 0.001) and depression (p < 0.001). Patients with depression at baseline were also those for whom a significantly greater increase in MCS score during the 6 months of follow-up was observed.

Conclusion
Our findings highlight the importance of screening early psychological distress and considering other factors associated with HRQoL changes in outpatients after the first 3-month period of treatment for substance use disorder.
Physiological assessment of orthostatic intolerance in chronic fatigue syndrome
Authors: Natelson Benjamin H. , Lin Jin-Mann S. , Blate Michelle , Khan Sarah , Chen Yang , Unger Elizabeth R. 
Published: February 2022

Abstract
Background
Orthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end tidal CO2 (eTCO2). An abnormal physiologic response to OC was identified in 60% of the 63 patients evaluated from one to three times over several years. Hypocapnia, either resting or induced by OC, was the most frequent abnormality, followed by postural orthostatic tachycardia.

Objective
Evaluate the physiologic response of patients with ME/CFS to a standardized OC.

Design
Respiratory and heart rate, blood pressure and eTCO2 were recorded twice at the end of 10-min supine rest and then every minute during the 10-min lean. Hypocapnia was eTCO2 ≤ 32 mmHg. Orthostatic tachycardia was heart rate increase ≥ 30 beats per minute compared with resting or ≥ 120 BPM. Orthostatic hypotension was decreased systolic pressure ≥ 20 mmHg from baseline. Tachypnea was respiratory rate of  ≥ 20 breaths per minute—either supine or leaning. Questionnaire data on symptom severity, quality of life and mood were collected at visit #2.

Patients
63 consecutive patients fulfilling the 1994 case definition for CFS underwent lean testing at first visit and then annually at visit 2 (n = 48) and 3 (n = 29).

Measures
Supine hypocapnia; orthostatic tachycardia, hypocapnia or hypotension.

Results
The majority of ME/CFS patients (60.3%, 38/63) had an abnormality detected during a lean test at any visit (51%, 50% and 45% at visits 1, 2 and 3, respectively). Hypocapnia at rest or induced by OC was more common and more likely to persist than postural orthostatic tachycardia. Anxiety scores did not differ between those with and without hypocapnia.

Conclusions
The 10-min lean test is useful in evaluation of OI in patients with ME/CFS. The most frequent abnormality, hypocapnia, would be missed without capnography.
Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of myalgic encephalomyelitis/chronic fatigue syndrome patients
Authors: Eaton-Fitch Natalie , Du Preez Stanley , Cabanas Hélène , Muraki Katsuhiko , Staines Donald , Marshall-Gradisnik Sonya 
Published: February 2022

AbstractBackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious disorder of unknown aetiology. While the pathomechanism of ME/CFS remains elusive, reduced natural killer (NK) cell cytotoxic function is a consistent immunological feature. NK cell effector functions rely on long-term sustained calcium (Ca2+) influx. In recent years evidence of transient receptor potential melastatin 3 (TRPM3) dysfunction supports the hypothesis that ME/CFS is potentially an ion channel disorder. Specifically, reports of single nucleotide polymorphisms, low surface expression and impaired function of TRPM3 have been reported in NK cells of ME/CFS patients. It has been reported that mu (µ)-opioid receptor (µOR) agonists, known collectively as opioids, inhibit TRPM3. Naltrexone hydrochloride (NTX), a µOR antagonist, negates the inhibitory action of µOR on TRPM3 function. Importantly, it has recently been reported that NTX restores impaired TRPM3 function in NK cells of ME/CFS patients.MethodsLive cell immunofluorescent imaging was used to measure TRPM3-dependent Ca2+influx in NK cells isolated from n = 10 ME/CFS patients and n = 10 age- and sex-matched healthy controls (HC) following modulation with TRPM3-agonist, pregnenolone sulfate (PregS) and TRPM3-antaognist, ononetin. The effect of overnight (24 h) NTX in vitro treatment on TRPM3-dependent Ca2+influx was determined.ResultsThe amplitude (p < 0.0001) and half-time of Ca2+response (p < 0.0001) was significantly reduced at baseline in NK cells of ME/CFS patients compared with HC. Overnight treatment of NK cells with NTX significantly improved TRPM3-dependent Ca2+influx in ME/CFS patients. Specifically, there was no significance between HC and ME/CFS patients for half-time response, and the amplitude of Ca2+influx was significantly increased in ME/CFS patients (p < 0.0001).ConclusionTRPM3-dependent Ca2+influx was restored in ME/CFS patients following overnight treatment of isolated NK cells with NTX in vitro. Collectively, these findings validate that TRPM3 loss of function results in altered Ca2+influx supporting the growing evidence that ME/CFS is a TRP ion channel disorder and that NTX provides a potential therapeutic intervention for ME/CFS.
High sensitivity C-reactive protein and glycated hemoglobin levels as dominant predictors of all-cause dementia: a nationwide population-based cohort study
Authors: Fan Yen-Chun , Chou Chia-Chi , Bintoro Bagas Suryo , Chien Kuo-Liong , Bai Chyi-Huey 
Published: February 2022

Abstract
Background
Chronic inflammation might play a major role in the pathogenesis linking diabetes mellitus (DM) to cognition. In addition, DM might be the main driver of dementia risk. The purpose of the present study was to evaluate whether inflammation, glycation, or both are associated with the risk of developing all-cause dementia (ACD).

Methods
A nationwide population-based cohort study was conducted with 4113 participants. The data were obtained from the Taiwanese Survey on Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) in 2007, which was linked with the Taiwan National Health Insurance Research Database (NHIRD). The markers of inflammation, expressed as hs-CRP, and glycation, presented as HbA1c, were measured. High levels of hs-CRP and HbA1c were defined as values greater than or equal to the 66th percentile. Developed ACD was identified based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.

Results
During 32,926.90 person-years, 106 individuals developed ACD in up to 8 years of follow-up. The study participants were separated into four categories by the top tertiles of hs-CRP and HbA1c based on the 66th percentile: high levels of both hs-CRP and HbA1c, only high levels of hs-CRP, only high levels of HbA1c, and non-high levels of hs-CRP nor HbA1c. Those who with a high level of only hs-CRP had the higher hazard for developing ACD (adjusted HR = 2.58; 95% CI = 1.29 ~ 5.17; P = 0.007), followed by the group with a high level of only HbA1c (adjusted HR = 2.52; 95% CI = 1.34 ~ 4.74; P = 0.004) and the group with high levels of both hs-CRP and HbA1c (adjusted HR = 2.36; 95% CI = 1.20 ~ 4.62; P = 0.012). Among those aged less than 65 years, hs-CRP was the only significant predictor of ACD risk (P = 0.046), whereas it did not yield any significant result in the elderly.

Conclusions
A higher risk of developing ACD was found not only in patients with high levels of inflammation but also high levels of glycated hemoglobin. Future studies should focus on the clinical implementation of hs-CRP or HbA1c to monitor cognitive deficits.
Genetic mutation profiles and immune microenvironment analysis of pulmonary enteric adenocarcinoma
Authors: Xie Min , Chen Dong , Li Yong , Liu Xiansheng , Kuang Dong , Li Xiaochen 
Published: February 2022

Abstract
Background
Pulmonary enteric adenocarcinoma (PEAC) has distinctive clinical outcomes, radiographic, pathological and molecular characteristics. The prognosis of patients with PEAC was poor. However, molecular profiles and therapeutic biomarkers of PEAC remain elusive.

Methods
In the present study, the hospitalized patients with PEAC admitted to Tongji Hospital in Wuhan from January 1, 2014 to November 20, 2020 were retrospectively enrolled and followed until December 10, 2020. Comprehensive genomic profiling of tumor tissue from the PEAC patients were performed and compared with lung adenocarcinoma, colorectal cancer and metastatic colorectal carcinoma. Tumor immune microenvironment analysis were evaluated.

Results
There were 10 patients with PEAC enrolled. 70% of patients were male and the median age of onset was 63 years (interquartile range, 55–72). There were six early-stage patients (Stage IA to IIB) and four stage IV patients. Molecular analysis revealed the most common gene mutations included TP53 (57%, 4/7) and KRAS (57%, 4/7) mutations. There were 40% mutations occurred in genes encoding receptor tyrosine kinases (RTKs). 100% of patients (8/8) were microsatellite stability (MSS). The median level of TMB was 6.0 (interquartile range, 4.5–7.0) mutations/Mb. Three of 10 patients showed low PD-L1 expression (tumor proportion score < 10%) and the others were PD-L1 negative. A small subset of CD8+, CD3+, CD68+ T cells were observed and were mainly distributed in the cancer stroma.

Conclusion
This study demonstrated that PEAC was characterized by low-frequency RTK gene mutation, high KRAS mutation, low PD-L1 expression, low TMB, and low CD8+ T cells infiltration.
Morphological diversity of the tricuspid posterior leaflet affects surgical complexity for control of tricuspid regurgitation
Authors: Kawase Takumi , Takahashi Yosuke , Nishiya Kenta , Kishimoto Noriaki , Yamane Kokoro , Sakon Yoshito , Morisaki Akimasa , Fujii Hiromichi , Shibata Toshihiko 
Published: February 2022

Abstract
Objective
We investigated the effect of morphological diversity of the tricuspid valve with multiple posterior leaflets on the technical outcomes of tricuspid valve repair.

Methods
From April 2016 to November 2020, 141 patients were diagnosed with secondary tricuspid regurgitation associated with left heart disease and underwent tricuspid valve repair. We retrospectively analyzed the clinical and echocardiographic data of patients who underwent both preoperative and postoperative transthoracic echocardiography. We divided the patients into two groups according to the surgical technique used to treat tricuspid regurgitation: ring annuloplasty alone (Group 1, n = 109) or additional approximation of leaflet edges (edge-to-edge repair) with ring annuloplasty (Group 2, n = 32). We measured the morphological diversity of the tricuspid valve during the operation in all patients.

Results
The preoperative tricuspid regurgitation score was higher in Group 2 than in Group 1 (2.1 ± 0.78 vs. 1.6 ± 0.7, respectively; p = 0.0046), and Group 2 contained more patients with two posterior leaflets than Group 1 [20 (63%) vs. 36 (33%), respectively; p = 0.003]. The univariate and multivariate logistic regression analyses showed that the presence of two posterior leaflets was an independent risk factor for additional procedures during tricuspid valve repair (odds ratio, 2.6; 95% confidence interval, 1.1–6.1; p = 0.033).

Conclusions
Additional procedures to reduce tricuspid regurgitation were required more frequently in patients with two posterior leaflets of the tricuspid valve. The morphological diversity of two posterior leaflets is a potential risk factor for a more complicated tricuspid repair.
Challenges and improvement needs in the care of patients with central diabetes insipidus
Authors: Teare H. , Argente J. , Dattani M. , Leger J. , Maghnie M. , Sherlock M. , Ali G.-C. , Francombe J. , Marjanovic S. 
Published: February 2022

AbstractCentral diabetes insipidus (CDI) is a rare condition, with significant impact on patient health and well-being. It is a chronic condition which usually requires meticulous long-term care. It can affect both children and adults. There is limited literature considering the needs and challenges inherent in providing high quality care to patients with CDI, across the care pathway. This paper seeks to address this gap by providing a unique and well-rounded understanding of clinical and healthcare systems-related challenges. It draws on insights from the literature, from direct clinical experience contributed by five clinicians as co-authors (providing insights from France, Ireland, Italy, Spain and the United Kingdom), and from patient perspectives provided through interviews with patient representatives from three patient organisations. We identify clinical challenges related to the diagnosis of CDI, including differentiating between other similar conditions and determining the underlying aetiology. Treatment is challenging, given the need to tailor medication to each patient’s needs and ongoing management is required to ensure that patients continue to respond adequately to treatment. Ongoing support is required when patients switch between formulations. We also identify healthcare systems challenges related to limited awareness of CDI amongst primary care physicians and general paediatricians, and the need for highly skilled specialist care and appropriate workforce capacity. There is also a significant need for raising awareness and for the education of both healthcare professionals and patients about different aspects of CDI, with the aim of supporting improved care and effective patient engagement with healthcare professionals. We reflect on this information and highlight improvement opportunities. These relate to developing guidance to support patients, carers, primary care physicians and general paediatricians to identify clinical features earlier, and to consider CDI as a possible diagnosis when a patient presents with suggestive symptoms.
Risk factors for pregnancy-related clinical outcome in myasthenia gravis: a systemic review and meta-analysis
Authors: Su Manqiqige , Liu Xiaoqing , Wang Liang , Song Jie , Zhou Zhirui , Luo Sushan , Zhao Chongbo 
Published: February 2022

Abstract
Objective
Myasthenia gravis (MG) is an autoimmune disorder that frequently affects females at reproductive age. Herein, we aimed to assess the associations of clinical factors with pregnancy-related outcome in MG.

Methods
We searched PubMed and EMBASE for case–control and cohort studies that reported the MG status during or after pregnancy and relevant clinical variables. The data was extracted in proportions and odds ratios (ORs) with 95% confidence intervals (CIs) in subsequent meta-analysis.

Results
Fifteen eligible articles reporting on 734 pregnancies with 193 worsening and 51 improved episodes were included out of 1765 records. The estimated worsening proportions in total, antepartum and postpartum periods were 0.36 (95% CI 0.25–0.40), 0.23 (95% CI 0.14–0.34) and 0.11 (95% CI 0.04–0.22) respectively. The proportion of pregnancy-related improvement in enrolled patients was 0.28 (95% CI 0.17–0.40), with 0.07 (95% CI 0.00–0.28) during pregnancy and 0.14 (95% CI 0.02–0.34) after pregnancy. No significant associations were disclosed between the clinical factors and MG worsening. Thymectomy before delivery is a strong predictor for MG improvement in postpartum period (OR 4.85, 95% CI 1.88–12.50, p = 0.001).

Conclusion
The total proportion of pregnancy-related MG worsening and improvement in MG was 0.36 (95% CI 0.25–0.40) and 0.28 (95% CI 0.17–0.40), respectively. Thymectomy before the delivery may aid in clinical improvements associated with pregnancy. Future prospective cohort studies are required to determine more relevant factors.
Assessing the role of blood pressure in amyotrophic lateral sclerosis: a Mendelian randomization study
Authors: Xia Kailin , Zhang Linjing , Tang Lu , Huang Tao , Fan Dongsheng 
Published: February 2022

Abstract
Background
Observational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS). It remains unclear whether this association is causal. The authors employed a bidirectional two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between BP and ALS. Genetic proxies for systolic blood pressure (SBP), diastolic blood pressure (DBP), antihypertensive drugs (AHDs), ALS, and their corresponding genome-wide association study (GWAS) summary datasets were obtained from the most recent studies with the largest sample sizes. The inverse variance weighted (IVW) method was adopted as the main approach to examine the effect of BP on ALS and four other MR methods were used for sensitivity analyses. To exclude the interference between SBP and DBP, a multivariable MR approach was used.

Results
We found that genetically determined increased DBP was a protective factor for ALS (OR = 0.978, 95% CI 0.960–0.996, P = 0.017) and that increased SBP was an independent risk factor for ALS (OR = 1.014, 95% CI 1.003–1.025, P = 0.015), which is supported by sensitivity analyses. The use of calcium channel blocker (CCB) showed a causal relationship with ALS (OR = 0.985, 95% CI 0.971–1.000, P = 0.049). No evidence was revealed that ALS caused changes in BP.

Conclusions
This study provides genetic support for a causal effect of BP and ALS that increased DBP has a protective effect on ALS, and increased SBP is a risk factor for ALS, which may be related to sympathetic excitability. Blood pressure management is essential in ALS, and CCB may be a promising candidate.
Is it possible to implement a rare disease case-finding tool in primary care? A UK-based pilot study
Authors: Buendia Orlando , Shankar Sneha , Mahon Hadley , Toal Connor , Menzies Lara , Ravichandran Pradeep , Roper Jane , Takhar Jag , Benfredj Rudy , Evans Will 
Published: February 2022

Abstract
Introduction
This study implemented MendelScan, a primary care rare disease case-finding tool, into a UK National Health Service population. Rare disease diagnosis is challenging due to disease complexity and low physician awareness. The 2021 UK Rare Diseases Framework highlights as a key priority the need for faster diagnosis to improve clinical outcomes.

Methods and results
A UK primary care locality with 68,705 patients was examined. MendelScan encodes diagnostic/screening criteria for multiple rare diseases, mapping clinical terms to appropriate SNOMED CT codes (UK primary care standardised clinical terminology) to create digital algorithms. These algorithms were applied to a pseudo-anonymised structured data extract of the electronic health records (EHR) in this locality to "flag" at-risk patients who may require further evaluation. All flagged patients then underwent internal clinical review (a doctor reviewing each EHR flagged by the algorithm, removing all cases with a clear diagnosis/diagnoses that explains the clinical features that led to the patient being flagged); for those that passed this review, a report was returned to their GP. 55 of 76 disease criteria flagged at least one patient. 227 (0.33%) of the total 68,705 of EHR were flagged; 18 EHR were already diagnosed with the disease (the highlighted EHR had a diagnostic code for the same RD it was screened for, e.g. Behcet’s disease algorithm identifying an EHR with a SNOMED CT code Behcet's disease). 75/227 (33%) EHR passed our internal review. Thirty-six reports were returned to the GP. Feedback was available for 28/36 of the reports sent. GP categorised nine reports as "Reasonable possible diagnosis" (advance for investigation), six reports as "diagnosis has already been excluded", ten reports as "patient has a clear alternative aetiology", and three reports as "Other" (patient left study locality, unable to re-identify accurately). All the 9 cases considered as "reasonable possible diagnosis" had further evaluation.

Conclusions
This pilot demonstrates that implementing such a tool is feasible at a population level. The case-finding tool identified credible cases which were subsequently referred for further investigation. Future work includes performance-based validation studies of diagnostic algorithms and the scalability of the tool.
Long-term clinical efficacy of topical treatment with recombinant human nerve growth factor in neurotrophic keratopathy: a novel cure for a rare degenerative corneal disease?
Authors: Bruscolini Alice , Marenco Marco , Albanese Giuseppe Maria , Lambiase Alessandro , Sacchetti Marta 
Published: February 2022

Abstract
Background
Neurotrophic keratopathy (NK) is a rare, degenerative ocular disease characterized by reduction or loss of corneal sensitivity and development of non-healing corneal epithelial defects and ulcers. Cenegermin, a recombinant human nerve growth factor (rhNGF) eye drop solution, is the first drug approved for the treatment of NK. The aim of our study is to evaluate the long-term efficacy of this innovative topical treatment in patients with NK.

Methods
Retrospective, consecutive, observational case series study from a single-center setting (Department of Sense Organs, University Sapienza of Rome, Rome, Italy). 18 patients with diagnosis of stage 2 or 3 NK, treated with Cenegermin 20 mcg/ml eye drops were followed for up to 48 months. Recurrence of lesion during follow-up was evaluated at 12, 24, 36, and 48 months. In addition, corneal sensitivity, Schirmer tear test, and visual acuity (VA) were recorded at baseline, end of treatment, and at 12, 24, 36, and 48 months.

Results
Three patients experienced recurrence of persistent epithelial defects (PEDs) within 12 months and one patient experienced recurrence of a corneal ulcer within 36 months. Corneal sensitivity was significantly improved at all timepoints (P < 0.05). Significant improvements in visual acuity and tear production were seen at the completion of treatment as well as at 12, 24, and 36 months (P < 0.05) when compared to baseline.

Conclusions
A single 8-week treatment regimen of Cenegermin eye drops has clinical efficacy that can persist for up to 48 months. The long-term clinical utility of treatment with Cenegermin for NK was demonstrated through the low rate of lesion recurrence along with improvements in corneal sensitivity and tear production.