bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing Age-calibrated Normative PROMIS Scores for Hand and Upper Extremity Clinic
Authors: Yedulla Nikhil R. , Wilmouth Carson T. , Franovic Sreten , Hazime Alaa A. , Hudson Jared T. , Day Charles S. 
Published: August 2021

Background:
The purpose of our study is to investigate differences in normative PROMIS upper extremity function (PROMIS-UE), physical function (PROMIS-PF), and pain interference (PROMIS-PI) scores across age cohorts in individuals without upper extremity disability.

Methods:
Individuals without upper extremity disability were prospectively enrolled. Subjects were administered PROMIS-UE, PROMIS-PF, and PROMIS-PI forms. Retrospective PROMIS data for eligible subjects were also utilized. The enrolled cohort was divided into age groups: 20–39, 40–59, and 60–79 years old. ANOVA, ceiling and floor effect analysis, and kurtosis and skewness statistics were performed to assess PROMIS scores trends with age.

Results:
This study included 346 individuals. In the 20–39 age group, mean PROMIS scores were 56.2 ± 6.1, 59.8 ± 6.9, and 43.1 ± 6.7 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. In the “40–59” age group, mean PROMIS computer adaptive test scores were 53.3 ± 7.5, 55.3 ± 7.6, and 46.6 ± 7.8 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. In the 60–79 age group, mean PROMIS scores were 48.4 ± 7.6, 48.5 ± 5.6, and 48.7 ± 6.9 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. Differences in mean PROMIS scores were significant across all PROMIS domains and age cohorts (P < 0.001).

Conclusion:
Younger individuals without hand or upper extremity disability show higher normative PROMIS-UE and PROMIS-PF scores and lower PROMIS-PI scores, indicating greater function and less pain than older counterparts. A universal reference PROMIS score of 50 appears suboptimal for clinical assessment and decision-making in the hand and upper extremity clinic.
Time-of-Year Variation in Intraocular Pressure
Authors: Morettin Christina E. , Roberts Daniel K. , Newman Tricia L. , Yang Yongyi , McMahon Janice M. , Roberts Mary Flynn , Teitelbaum Bruce A. , Winters Janis E. 
Published: August 2021

Précis:
In this study conducted in Chicago, IL, intraocular pressure (IOP) level was found to have a subtle, but measurable, annual pattern. Reasonable evidence is presented for a time-of-year variation in IOP. Adequate numbers of subjects must be studied to detect this small variation.

Purpose:
The aim was to investigate the relationship between IOP and time of year.

Methods:
During a separate investigation, patients from 2011 to 2018 (dataset A, N=3041) in an urban, academic facility in Chicago, IL received an examination that included Goldmann applanation tonometry. Regression analyses assessed the relationship between time of year and IOP. Two additional datasets, 1 collected in a similar manner during 1999 and 2002 (dataset B, N=3261) and another consisting of all first visits during 2012 and 2017 (dataset C, N=69,858), were used to confirm and further investigate trends.

Results:
For dataset A, peak mean IOP occurred in December/January (15.7±3.7/15.7±3.8 mm Hg) and lowest in September (14.5±3.1 mm Hg). The analysis suggested conventional quarterly analysis (January to March, etc.) can conceal time-of-year relationships because of inadequate statistical power and timing of IOP variation. Multiple linear regression analysis, with a November-to-October reordering, detected an annual, downward IOP trend (P<0.0001). Analysis of dataset B confirmed this trend (P<0.001). Fourier analysis on datasets A and B combined supported a 12-month IOP cycle for right/left eyes (P=0.01/P=0.005) and dataset C provided stronger evidence for an annual periodicity (P<0.0001). Harmonics analysis of dataset C showed a repeating pattern where IOP trended downward around April, and then back upward around October.

Conclusions:
This analysis strongly supports a demonstrable annual, cyclical IOP pattern with a trough to peak variation of ≈1 mm Hg, which has a seasonal relationship.
Long-term cumulative incidence of metachronous advanced colorectal neoplasia after colonoscopy and a novel risk factor: a cohort study
Authors: Omata Fumio , Deshpande Gautam A. , Suzuki Hidekazu , Hayashi Kuniyoshi , Ishii Naoki , Matoba Kohei , Ohmuro Akemi , Rai Fumie , Takashima Misako , Fukuda Katsuyuki , Masuda Katsunori , Kumakura Yasuhisa 
Published: August 2021

Background and aim
Long-term cumulative incidence of and risk factors for metachronous advanced colorectal neoplasia, including both advanced colorectal adenoma (≥10 mm, or with villous or high-grade dysplasia) and colorectal cancer, are critical for surveillance strategies. The aim of this study was to determine the cumulative incidence of metachronous advanced colorectal neoplasia and its risk factors.

Methods
A retrospective cohort study was conducted on 6720 consecutive individuals who underwent general health check-ups and colonoscopy. Colorectal adenomas at initial colonoscopy were categorized as low-risk (1–2 small [<10 mm] tubular adenomas) or high-risk adenoma (≥3 tubular adenomas of any size; at least one adenoma ≥10 mm; or villous adenoma or adenoma with high-grade dysplasia). Kaplan–Meier estimates and hazard ratio by Cox-proportional hazard regression were calculated.

Results
The cumulative incidence (95% confidence interval [CI]) of metachronous advanced colorectal neoplasia at 5 and 10 years was 5.7% [4.6–7.1], and 11% [8.9–14] in the low-risk adenoma group, and 10% [8.6–13], and 17% [14–21] in high-risk adenoma group, respectively. Adjusted hazard ratio [95% CI] of low-risk adenoma (vs. no colorectal adenoma), high-risk adenoma (vs. no colorectal adenoma), current smoking and positive fecal immunochemical test were 1.34 [1.04–1.74], 1.94 [1.48–2.55], 1.55 [1.2–2.02] and 1.69 [1.35–2.1], respectively. Adjusted hazard ratio [95% CI] of positive fecal immunochemical test was 1.88 [1.29–2.74] in those with normal colonoscopy.

Conclusions
Both low-risk and high-risk adenomas confer substantial risk for metachronous advanced colorectal neoplasia at 10 years. Positive fecal immunochemical test was a significant risk factor for metachronous advanced colorectal neoplasia despite normal colonoscopy.
Prediction of high-risk esophageal varices in patients with compensated cirrhosis using albumin-bilirubin-platelet score
Authors: Abd elbaser Elsayed Saad , Sharaf Ahmed Lotfy , Farag Alaa A. 
Published: August 2021

Background
Despite the fact that endoscopy is the gold standard for screening of high-risk varices (HRVs) in patients with compensated cirrhosis, it is invasive, costly and not necessary for all patients. So, noninvasive tests can replace endoscopy. We aimed at evaluating the albumin-bilirubin-platelet (ALBL-PLT) score as a noninvasive test in predicting HRVs in compensated cirrhotic patients versus Baveno VI and extended Baveno VI criteria.

Methods
patients with compensated cirrhosis (n = 204) were included. Laboratory parameters, esophagogastroduodenoscopy (EGD) and liver stiffness measurement by transient elastography were done. Classification of patients according to the status of HRVs was done. We compared both groups on the basis of ALBL-PLT score, Baveno VI and extended Baveno VI criteria.

Results
Among the total patients, 96/204 (47%) patients had HRVs. They have higher liver stiffness measurement than those without HRVs (33 ± 13.1 versus 19.3 ± 8.25, CI, −19.94, −7.31, P value <0.001). Also, all HRVs patients have an ALBL-PLT score of more than 3. The area under the receiver operating characteristic curve for the ALBL-PLT score is higher than that for Baveno VI and extended Baveno VI criteria (0.894 versus 0.722 and 0.792, respectively).

Conclusion
ALBL-PLT score of more than three has a good predictive value in predicting HRVs among compensated cirrhotic patients.
Ustekinumab concentrations shortly after escalation to monthly dosing may identify endoscopic remission in refractory Crohn’s disease
Authors: Hanžel Jurij , Koželj Matic , Špes Hlastec Ana , Kurent Tina , Sever Nejc , Zdovc Jurij , Smrekar Nataša , Novak Gregor , Štabuc Borut , Grabnar Iztok , Drobne David 
Published: August 2021

Objectives
Some patients with Crohn’s disease do not achieve remission with the approved maintenance dosing of ustekinumab every 8 weeks, possibly due to insufficient drug exposure. We aimed to study the exposure–response relationship for endoscopic remission and biomarker normalization with ustekinumab dose escalation to every 4 weeks.

Methods
Out of 135 consecutive patients, 44 with active Crohn’s disease despite standard maintenance dosing [at least one of C-reactive protein (CRP) >5 mg/L, fecal calprotectin >100 mg/kg, simple endoscopic score (SES) for Crohn’s disease >3] underwent dose escalation to every 4 weeks. Subsequent endoscopic remission (SES-CD ≤3 without ulceration) and biomarker normalization were compared against ustekinumab concentrations.

Results
Dose escalation led to endoscopic remission in 28.6% (8/28), CRP normalization 29.2% (7/24) and fecal calprotectin normalization 51.7% (15/29) of patients. Ustekinumab concentrations after escalation were higher in patients with endoscopic remission (6.90 vs. 4.29 mg/L; P = 0.025) and fecal calprotectin normalization (6.65 vs. 3.74 mg/L; P = 0.001). A threshold of 6.00 mg/L identified endoscopic remission [area under the receiver operating curve (AUROC): 0.775; 95% confidence interval (CI), 0.551–0.999), a threshold of 4.40 mg/L (AUROC 0.755; 95% CI, 0.545–0.964) two months after escalation identified patients with fecal calprotectin normalization at the end of follow-up. Concentrations <3.5 mg/L after escalation precluded endoscopic remission or biomarker normalization.

Conclusion
Endoscopic remission was associated with higher ustekinumab concentrations after dose escalation. Patients with concentrations <3.5 mg/L after dose escalation are unlikely to achieve endoscopic remission or biomarker normalization.
Comparison of long-term outcomes of balloon angioplasty with or without stent placement for hepatic vein type Budd-Chiari syndrome
Authors: Sun Xuedong , Zhang Jinlong , Duan Feng , Wang Maoqiang 
Published: August 2021

Purpose
To compare percutaneous transluminal balloon angioplasty (PTBA) alone with PTBA plus stent placement for Budd-Chiari syndrome (BCS) patients with short-segmental obstruction of hepatic vein.

Methods
Between May 2001 and December 2010, 91 hepatic vein type BCS patients (mean age, 32.8 ± 10.8; M:F ratio 50:41) were included and divided into two groups (PTBA alone, as group A, n = 48; PTBA plus stent, as group B, n = 43). The incidence of restenosis, long-term patency, and survival were evaluated.

Results
All 91 patients were successfully treated with hepatic vein recanalization. During follow-up period (median 161 months, range: 84–234), group B had a significantly higher proportion of hepatic vein restenosis (56%, 24/43) than group A (33%, 16/48; P < 0.05). Cumulative primary patency rates at 1, 5, 10, 15 years were 96%, 81%, 69%, 65% and 91%, 60%, 47%, 47% in group A and group B, respectively (log-rank P < 0.05). Secondary technical success rates of target hepatic vein were 93% and 57% in group A and group B, respectively (P < 0.05). Clinical complete response rates were 94% and 86% in group A and group B, respectively (P > 0.05). The 15-year cumulative survival rates were 98% and 95% in group A and group B, respectively (P > 0.05). Major procedure-related complications occurred in 3 (3%) patients (1 in group A, 2 in group B).

Conclusions
Hepatic vein recanalization is safe and efficient for hepatic vein type BCS patients with hepatic vein short segmental obstruction. Restenosis after hepatic vein stenting is more common and difficult to manage than that after hepatic vein balloon angioplasty alone.
Amyotrophic lateral sclerosis is a systemic disease: peripheral contributions to inflammation-mediated neurodegeneration
Authors: Appel Stanley H. , Beers David R. , Zhao Weihua 
Published: August 2021

Purpose of review
Neuroinflammation is an important mediator of the pathogenesis of disease in amyotrophic lateral sclerosis (ALS). Genetic mutations such as C9orf72 have begun to define the numerous cell autonomous pathways that initiate motor neuron injury. Yet, it is the signalling to surrounding glia and peripherally derived immune cells that initiates the noncell autonomous inflammatory process and promotes self-propagating motor neuron cell death. The purpose of this review is to explore the systemic immune/inflammatory contributions to the pathogenesis of ALS: what are the peripheral pro-inflammatory signatures, what initiates their presence and do they represent potential therapeutic targets.

Recent findings
In ALS, motor neuron cell death is initiated by multiple cell autonomous pathways leading to misfolded proteins, oxidative stress, altered mitochondria, impaired autophagy and altered RNA metabolism, which collectively promote noncell autonomous inflammatory reactivity. The resulting disease is characterized by activated microglia and astrocytes as well as peripherally derived pro-inflammatory innate and adaptive immune cells. In this unrelenting disorder, circulating blood monocytes and natural killer cells are pro-inflammatory. Furthermore, regulatory T lymphocytes are dysfunctional, and pro-inflammatory cytokines and acute phase proteins are elevated.

Summary
The collective dysregulation of cells and cytokines in patients with ALS accurately reflect increased disease burdens, more rapid progression rates and reduced survival times, reinforcing the concept of ALS as a disorder with extensive systemic pro-inflammatory responses. These increased systemic pro-inflammatory immune constituents provide potentially meaningful therapeutic targets.
TMCC2 Associates with Alzheimer’s Disease Pathology in the Human Brain
Authors: Hopkins Paul C. R. , Troakes Claire , King Andrew , Tear Guy 
Published: August 2021

AbstractTransmembrane and Coiled-Coil 2 (TMCC2) is a protein that forms complexes with both apolipoprotein E (apoE) and the amyloid protein precursor (APP), two proteins central to the etiology of Alzheimer’s disease (AD). Here we have carried out the first investigation of TMCC2 expression in the human brain, where TMCC2 immunoreactivity is primarily neuronal. We also examined TMCC2 localization in late onset AD brains,early onset AD cases bearing a mutation in APP, and in Down syndrome cases. TMCC2 immunoreactivity is closely associated with APP immunoreactivity in both control and AD cases. In all AD cases examined, TMCC2 associated with dense core senile plaques and adjacent dystrophic neurites, but not with amyloid surrounding the core, nor with diffuse amyloid plaques or neurofibrillary tangles. In Down syndrome, we found dystrophic neurites in senile plaques that were positive for amyloid and TMCC2, but not for APP, in addition to the APP- and TMCC2-positive dense cores. Western blot analysis revealed TMCC2 exists as at least three protein isoforms. The relative abundance of the isoforms varies in the temporal gyrus and cerebellum, the relative proportions of which were influenced by APOE and/or dementia status.Taken together, these observations are consistent with the evolutionarily conserved interactions between APP and TMCC2 and suggest cooperation betweenTMCC2 and APP in the normal and AD brain. These findings thus support a role for TMCC2 as a mediator of the impact of apoE on AD pathogenesis.
Combining Plasma Extracellular Vesicle Let-7b-5p, miR-184 and Circulating miR-22-3p Levels for NSCLC Diagnosis and for Predicting Drug Resistance
Authors: Vadla G. P. , Daghat B. , Garcia A. , Perez G. , Ahmad V. , Patterson N. , Manjunath Y. , Kaifi J.T. , Li G. , Chabu C.Y. 
Published: August 2021

AbstractLow-dose computed tomography (LDCT) Non-Small Cell Lung (NSCLC) screening is associated with high false-positive rates, leading to unnecessary expensive and invasive follow ups. There is a need for minimally invasive approaches to improve the accuracy of NSCLC diagnosis. Plasma extracellular vesicle (EV) and circulating microRNA (miRNA) have been proposed as cancer screening biomarkers. However, the identification of highly sensitive and broadly predictive core miRNA signatures remains a challenge. Also, how these systemic and diverse miRNAs impact cancer drug response is not well understood. Using an integrative approach, we examined plasma EV and circulating miRNA isolated from NSCLC patients versus screening controls with a similar risk profile. We found that combining EV (Hsa-miR-184, Let-7b-5p) and circulating (Hsa-miR-22-3p) miRNAs abundance robustly discriminates between NSCLC patients and high-risk cancer-free controls. Diagnosed NSCLC patients harboring sensitizing mutations in epidermal growth factor receptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI). Nearly all patients develop TKI resistance via complex mechanisms and progress. We found that Hsa-miR-22-3p, Hsa-miR-184, and Let-7b-5p functionally converge on WNT/βcatenin and mTOR/AKT signaling axes, known cancer therapy resistance signals. Targeting Hsa-miR-22-3p and Hsa-miR-184 desensitized EGFR-mutated (T790M, L578R) NSCLC cells to Osimertinib. These findings suggest that the expression levels of circulating hsa-miR-22-3p combined with EV hsa-miR-184 and Let-7b-5p levels potentially define a core biomarker signature for improving the accuracy of NSCLC diagnosis. Importantly, these biomarkers have the potential to enable prospective identification of patients who are at risk of responding poorly to Osimertinib alone but likely to benefit from Osimertinib/AKT blockade combination treatments.
Ten Ostreobium (Ulvophyceae) strains from Great Barrier Reef corals as a resource for algal endolith biology and genomics
Authors: Pasella Marisa M. , Lee Ming-Fen Eileen , Marcelino Vanessa R. , Willis Anusuya , Verbruggen Heroen 
Published: August 2021

ABSTRACTOstreobium is a genus of siphonous green algae that lives as an endolith in carbonate substrates under extremely limited light conditions and has recently been gaining attention due to its roles in reef carbonate budgets and its association with reef corals. Knowledge about this genus remains fairly limited due to the scarcity of strains available for physiological studies. Here, we report on 10 strains of Ostreobium isolated from coral skeletons from the Great Barrier Reef. Phenotypic diversity showed differences in the gross morphology and in few structures. Phylogenetic analyses of the tufA and rbcL put the strains in the context of the lineages identified previously through environmental sequencing. The chloroplast genomes of our strains are all around 80k bp in length and show that genome structure is highly conserved, with only a few insertions (some containing putative protein-coding genes) differing between the strains. The addition of these strains from the Great Barrier Reef to our toolkit will help develop Ostreobium as a model species for endolithic growth, low-light photosynthesis and coral-algal associations.
pyFoldX: enabling biomolecular analysis and engineering along structural ensembles
Authors: Radusky Leandro G. , Serrano Luis 
Published: August 2021

AbstractRecent years have seen an increase in the number of structures available, not only for new proteins but also for the same protein crystallized with different molecules and proteins. While protein design software have proven to be successful in designing and modifying proteins, they can also be overly sensitive to small conformational differences between structures of the same protein. To cope with this, we introduce here pyFoldX, a python library that allows the integrative analysis of structures of the same protein using FoldX, an established forcefield and modeling software. The library offers new functionalities for handling different structures of the same protein, an improved molecular parametrization module, and an easy integration with the data analysis ecosystem of the python programming language.Availability and implementationpyFoldX is an open-source library that uses the FoldX software for energy calculations and modelling. The latter can be downloaded upon registration in http://foldxsuite.crg.eu/ and is free of charge for academics. Full details on installation, tutorials covering the library functionality, and the scripts used to generate the data and figures presented in this paper are available at https://github.com/leandroradusky/pyFoldX.
Leptin Signalling in the Ovary of Diet-Induced Obese Mice Regulates Activation of Nod-Like Receptor Protein 3 Inflammasome
Authors: Adamowski Marek , Wołodko Karolina , Oliveira Joana , Castillo-Fernandez Juan , Murta Daniel , Kelsey Gavin , Galvão António M. 
Published: August 2021

1AbstractObesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterise levels of Nod-Like Receptor Protein 3 (NLRP3) inflammasome activation during obesity progression in the mouse ovaries and liver and test the putative role of leptin on its regulation. C57BL/6J mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for oestrous cycle synchronisation and ovaries collection. In diet-induced obesity (DIO) model, mice were fed chow diet (CD) or high fat diet (HFD) for 4 or 16 weeks (wk), whereas in hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16L) or saline (16C) and in the genetic obese leptin-deficient ob/ob (+/? and -/-) animals were fed CD for 4wk. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. In DIO protocol, protein expression of NLRP3 inflammasome components was increased in 4wk HFD, but decreased in 16wk HFD. Moreover LEPT and ob/ob models revealed NLRP3 and IL-1β upregulation in 16L and downregulation in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4wk HFD modulating NLRP3 inflammasome. Moreover analysis in the liver showed upregulation of NLRP3 protein only after 16wk HFD, but also the downregulation of NLRP3 protein in ob/ob-/-. We showed the link between leptin signalling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.
A Synthetic Genetic Reversible Feynman Gate in a Single E.coli Cell and its Application in Bacterial to Mammalian Cell Information Transfer
Authors: Srivastava Rajkamal , Sarkar Kathakali , Bonnerjee Deepro , Bagh Sangram 
Published: August 2021

AbstractReversible computing is a nonconventional form of computing where the inputs and outputs are mapped in a unique one-to-one fashion. Reversible logic gates in single living cells have not been demonstrated. Here, we created a synthetic genetic reversible Feynman gate in a single E.coli cell. The inputs were extracellular chemicals, IPTG and aTc and the outputs were two fluorescence proteins EGFP and E2-Crimson. We developed a simple mathematical model and simulation to capture the essential features of the genetic Feynman gate and experimentally demonstrated that the behavior of the circuit was ultrasensitive and predictive. We showed an application by creating an intercellular Feynman gate, where input information from bacteria was computed and transferred to HeLa cells through shRNAs delivery and the output signals were observed as silencing of native AKT1 and CTNNB1 genes in HeLa cells. Given that one-to-one input-output mapping, such reversible genetic systems might have applications in diagnostics and sensing, where compositions of multiple input chemicals could be estimated from the outputs.