bluuebunny/crossref_metadata_2025_split huggingface dataset:
The End of the Formal Rehabilitation Is Not the End of Rehabilitation: Knee Function Deficits Remain After Anterior Cruciate Ligament Reconstruction
Authors: Niederer Daniel , Keller Matthias , Wießmeier Max , Vogt Lutz , Stöhr Amelie , Schüttler Karl-Friedrich , Schoepp Christian , Petersen Wolf , Pinggera Lucia , Mengis Natalie , Mehl Julian , Krause Matthias , Janko Maren , Guenther Daniel , Engeroff Tobias , Ellermann Andree , Efe Turgay , Best Raymond , Groneberg David A. , Behringer Michael , Stein Thomas 
Published: January 2024

Objective: To rate athletes’ functional ability and return to sport (RTS) success at the end of their individual, formal, medically prescribed rehabilitation after anterior anterior cruciate ligament (ACL) reconstruction. Methods: In our prospective multicenter cohort study, 88 (42 females) adults aged 18–35 years after acute unilateral ACL rupture and subsequent hamstring grafting were included. All patients were prospectively monitored during their rehabilitation and RTS process until the end of their formal rehabilitation and RTS release. As outcome measures, functional hop and jump tests (front hop, balance hops, and drop jump screening test) and self-report outcomes (Knee Injury and Osteoarthritis Outcome Score, ACL-RTS after injury) were assessed. Literature-based cut-off values were selected to rate each performance as fulfilled or not. Results: At 7.5 months (SD 2.3 months) after surgery, the percentage of participants meeting the functional thresholds ranged from 4% (Knee Injury and Osteoarthritis Outcome Score SPORT) and over 44% (ACL-RTS after injury sum score) to 59% (Knee Injury and Osteoarthritis Outcome Score activities of all daily living) in the self-report and from 29% (Balance side hop) to 69% (normalized knee separation distance) in performance testing. Only 4% fulfilled all the cut-offs, while 45% returned to the same type and level of sport. Participants who successfully returned to their previous sport (type and level) were more likely to be “over-cut-off-performers.” Conclusions: The low share of the athletes who fulfilled the functional RTS criteria highlights the importance of continuing the rehabilitation measures after the formal completion to assess the need for and success of, inter alia, secondary-preventive therapies.
The
Helicobacter pylori
methylome is acid-responsive due to regulation by the two-component system ArsRS and the type I DNA methyltransferase HsdM1 (HP0463)
Authors: Zimmerman Elise H. , Ramsey Erin L. , Hunter Katherine E. , Villadelgado Sarah M. , Phillips Celeste M. , Shipman Ryan T. , Forsyth Mark H. 
Published: January 2024

ABSTRACT

In addition to its role in genome protection, DNA methylation can regulate gene expression. In this study, we characterized the impact of acidity, phase variation, and the ArsRS TCS on the expression of the Type I m6A DNA methyltransferase HsdM1 (HP0463) of
Helicobacter pylori
26695 and their subsequent effects on the methylome. Transcription of
hsdM
1 increases at least fourfold in the absence of the sensory histidine kinase ArsS, the major acid-sensing protein of
H. pylori. hsdM
1 exists in the phase-variable operon
hsdR
1-
hsdM
1. Phase-locking
hsdR
1 (HP0464), the restriction endonuclease gene, has significant impacts on the transcription of
hsdM
1. To determine the impacts of methyltransferase transcription patterns on the methylome, we conducted methylome sequencing on samples cultured at pH 7 or pH 5. We found differentially methylated motifs between these growth conditions and that deletions of
arsS
and/or
hsdM
1 interfere with the epigenetic acid response. Deletion of
arsS
leads to altered activity of HsdM1 and multiple other methyltransferases under both pH conditions indicating that the ArsRS TCS, in addition to direct effects on regulon transcription during acid acclimation, may also indirectly impact gene expression
via
regulation of the methylome. We determined the target motif of HsdM1 (HP0463) to be the complementary bipartite sequence pair 5′-TCA
m6A
VN
6
TGY-3′ and 3′-AGTN
6
GA
m6A
CA-5′. This complex regulation of DNA methyltransferases, and thus differential methylation patterns, may have implications for the decades-long persistent infection by
H. pylori
.

IMPORTANCE

This study expands the possibilities for complex, epigenomic regulation in
Helicobacter pylori
. We demonstrate that the
H. pylori
methylome is plastic and acid sensitive
via
the two-component system ArsRS and the DNA methyltransferase HsdM1. The control of a methyltransferase by ArsRS may allow for a layered response to changing acidity. Likely, an early response whereby ArsR~P affects regulon expression, including the methyltransferase
hsdM
1. Then, a somewhat later effect as the altered methylome, due to altered HsdM1 expression, subsequently alters the expression of other genes involved in acclimation. The intermediate methylation of certain motifs supports the hypothesis that methyltransferases play a regulatory role. Untangling this additional web of regulation could play a key role in understanding
H. pylori
colonization and persistence.
An assessment of the environmental sustainability of beef production in Canada
Authors: Aboagye Isaac A. , Valappil Gayathri , Dutta Baishali , Imbeault-Tétreault Hugues , Ominski Kim H. , Cordeiro Marcos R.C. , Kröbel Roland , Pogue Sarah J. , McAllister Tim A. 
Published: January 2024

This study assessed the environmental impacts of beef cattle production and their effects on the overall sustainability of Canadian beef production. Cradle to farm gate, cradle to processor’s gate, and cradle to consumer plate life cycle assessments were carried out to quantify greenhouse gases (GHG), resource use (i.e., water, land, and fuel), and potential water and air pollution (i.e., freshwater eutrophication, terrestrial acidification, and photochemical oxidants formation). Across the production chain, feed production had the greatest impact on most environmental indicators. The GHG intensity without dairy meat was estimated as 10.4 kg CO2-eq per kg of live weight (LW), corresponding to 32.8 kg CO2-eq per kg of consumed boneless beef. Including dairy meat reduced GHG intensity by 5.8% (0.6 kg CO2-eq kg LW–1) compared to when it was excluded. Other environmental metrics per kg of LW were 657 L, 38.7 m2 annual crop-eq, 0.4 kg oil-eq, 2.6 kg P-eq, 115.9 kg SO2-eq, and 8.7 kg NOx-eq for water use, land use, fossil fuel use, freshwater eutrophication, terrestrial acidification, and photochemical oxidants, respectively. Data provide benchmarks for use in future regional and national assessments that are designed to encourage the adoption of sustainable management practices that can lower the environmental footprint of Canadian beef production.
Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case–Control Study in Iran
Authors: Hadji Maryam , Rashidian Hamideh , Marzban Maryam , Rezaianzadeh Abbas , Ansari-Moghaddam Alireza , Bakhshi Mahdieh , Nejatizadeh Azim , Seyyedsalehi Monireh Sadat , Naghibzadeh-Tahami Ahmad , Haghdoost AliAkbar , Mohebbi Elham , Freedman Neal D. , Malekzadeh Reza , Etemadi Arash , Kamangar Farin , Weiderpass Elisabete , Pukkala Eero , Boffetta Paolo , Zendehdel Kazem 
Published: January 2024

Abstract

Background:
Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern.

Methods:
We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer.

Results:
We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69–1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16–2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21–4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11–6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24–4.42) than in current smokers (OR = 1.52; 95% CI, 0.72–3.15). All observed associations were consistently higher for urothelial histology.

Conclusions:
Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium.

Impact:
The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers.
See related In the Spotlight, p. 461
An Immune Gene Expression Risk Score for Distant Metastases after Radiotherapy for Cervical Cancer
Authors: Lukovic Jelena , Pintilie Melania , Han Kathy , Fyles Anthony W. , Bruce Jeffrey P. , Quevedo Rene , Pugh Trevor J. , Fjeldbo Christina S. , Lyng Heidi , Milosevic Michael F. 
Published: January 2024

Abstract

Purpose:
To develop an immune-based gene expression risk score to identify patients with cervical cancer at increased risk of distant metastases (DM).

Experimental Design:
Tumor biopsies were obtained from 81 patients prior to chemoradiotherapy. Whole-transcriptome RNA sequencing was performed (Illumina NextSeq500). Beginning with 4,723 immune-related genes, a 55-gene risk score for DM was derived using Cox modeling and principal component analysis. It was validated in independent cohorts of 274 patients treated at the Norwegian Radium Hospital (NRH) and 206 patients from The Cancer Genome Atlas (TCGA).

Results:
The risk score was predictive of DM (HR, 2.7; P &lt; 0.0001) and lower cause-specific survival (CSS) by univariate analysis (HR, 2.0; P = 0.0003) and multivariate analysis adjusted for clinical factors (DM HR, 3.0; P &lt; 0.0001; CSS HR, 2.2; P = 0.0004). The risk score predicted DM (HR, 1.4; P = 0.05) and CSS (HR, 1.48; P = 0.013) in the NRH cohort and CSS (HR, 1.4; P = 0.03) in TCGA cohort. Higher risk scores were associated with lower CIBERSORT estimates of tumor-infiltrating immune cells, including CD8 T cells and M1 and M2 macrophages (all P &lt; 0.001). Higher risk scores were associated with lower expression (all P &lt; 0.001) of important chemokines (CXCL12, CXCR4), IFN-regulated genes (IRF1, STAT1, IDO1), and immune checkpoint regulators (PD-1, PD-L1, CTLA-4).

Conclusions:
The immune metastatic risk score addresses important challenges in the treatment of cervical cancer—identifying patients at high risk of DM after radiotherapy. The findings of this study indicate that high tumor mutational burden and a “cold,” immune-excluded tumor microenvironment influence distant metastatic recurrence. Further validation of the risk score is needed.
Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study
Authors: Dauw Jeroen , Charaya Kristina , Lelonek Małgorzata , Zegri-Reiriz Isabel , Nasr Samer , Paredes-Paucar Cynthia P. , Borbély Attila , Erdal Fatih , Benkouar Riad , Cobo-Marcos Marta , Barge-Caballero Gonzalo , George Varghese , Zara Cornelia , Ross Noel T. , Barker Diane , Lekhakul Annop , Frea Simone , Ghazi Azmee M. , Knappe Dorit , Doghmi Nawal , Klincheva Milka , Fialho Inês , Bovolo Virginia , Findeisen Hajo , Alhaddad Imad A. , Galluzzo Alessandro , de la Espriella Rafael , Tabbalat Ramzi , Miró Òscar , Singh Jagdeep S. , Nijst Petra , Dupont Matthias , Martens Pieter , Mullens Wilfried 
Published: January 2024

Background:
The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload.

Methods:
ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms.

Results:

Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64;
P
<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52;
P
<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33;
P
<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87;
P
=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%;
P
=0.852).

Conclusions:
A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.
Directional Endothelial Communication by Polarized Extracellular Vesicle Release
Authors: Raju Sneha , Botts Steven R. , Blaser Mark C. , Abdul-Samad Majed , Prajapati Kamalben , Khosraviani Negar , Ho Tse Wing Winnie , Breda Leandro C.D. , Ching Crizza , Galant Natalie J. , Fiddes Lindsey , Wu Ruilin , Clift Cassandra L. , Pham Tan , Lee Warren L. , Singh Sasha A. , Aikawa Elena , Fish Jason E. , Howe Kathryn L. 
Published: January 2024

BACKGROUND:
Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments. Given their boundary location, we propose ECs use bidirectional release of distinct EV cargo in quiescent (healthy) and activated (atheroprone) states to communicate with cells within the circulation and blood vessel wall.

METHODS:
EVs were isolated from primary human aortic ECs (plate and transwell grown; ±IL [interleukin]-1β activation), quantified, visualized, and analyzed by miRNA transcriptomics and proteomics. Apical and basolateral EC-EV release was determined by miRNA transfer, total internal reflection fluorescence and electron microscopy. Vascular reprogramming (RNA sequencing) and functional assays were performed on primary human monocytes or smooth muscle cells±EC-EVs.

RESULTS:
Activated ECs increased EV release, with miRNA and protein cargo related to atherosclerosis. EV-treated monocytes and smooth muscle cells revealed activated EC-EV altered pathways that were proinflammatory and atherogenic. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, activated basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and smooth muscle cells, respectively, with functional assays and in vivo imaging supporting this concept.

CONCLUSIONS:
Demonstrating that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance the design of endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.
τὰ ἅγια εἰς λόγον εὐλογιῶν: Laodicea Canon 14 in its Phrygian Context
Authors: Stewart Alistair C. 
Published: January 2024

Abstract
The 14th canon of Laodicea, forbidding the exchange of τὰ ἅγια εἰς λόγον εὐλογιῶν, has never received a satisfactory explanation. This article suggests that it may be legislating against a local paschal custom which has become suspect due to its practice by Montanist communities.
Neonatal and Infant Illnesses and Health Seeking Behavior Among Hilly (Porja) Tribal Community: A Qualitative Observational Study
Authors: Samakya Srividhya , Pati Sanghamitra , Acharya Subhendu Kumar 
Published: January 2024

Objectives The study explores the health-seeking behavior for neonatal and infant illnesses of the Porja hilly tribe in Andhra Pradesh, India. Methods This study was a community-based qualitative observational study conducted from July 2022 to February 2023. In-depth interviews ( n = 31) were conducted with parents of neonates and infants. Two focus group discussions (involving 12 each) were conducted to validate the findings with other female family members such as, grandmothers. Data collection was carried out by using a semi-structured questionnaire on traditional practices and basic socio-demographic characteristics along with an in-depth interview guide for undertaking qualitative interviews. Results Qualitative findings were analyzed using the thematic framework approach, followed by the analysis of data from the field notes. Three themes (along with six sub-themes) were generated: (a) Early essential care, (b) Emergency of hospital care, (c) Effective Ethnomedical/Ritualistic Care (not requiring hospital care) which explained the tribal parents’ ways of care and treatment for their neonates and infants from various morbidity and mortality risks. Discussion Culture-specified traditional beliefs play crucial roles in shaping the neonatal and infant health of indigenous hilly tribal communities. Preserving the beneficial traditional methods and preventing harmful practices can help improve the overall child health status in such resource scanty settings with inadequate neonatal services.
Moringa oleifera Modulates MPTP-induced Mitochondrial Dysfunction in Parkinson’s Mouse Model: An in silico and in vivo Analysis
Authors: Singh Smriti , Keshri Priyanka Kumari , Mishra Vijaya Nath , Singh Surya Pratap 
Published: January 2024

Background: Parkinson’s disease (PD) is a movement-affecting neurodegenerative condition with an unclear etiology. Recent research suggests targeting poly-(adenosine 5-diphosphate-ribose) polymerase 1 (PARP1) as a potential therapeutic approach for PD treatment. Purpose: The purpose of this study is to assess the effect of an ethanolic extract of Moringa oleifera leaves (MOE) on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mouse model, with a specific focus on investigating its potential to mitigate the effects of α-synuclein toxicity, oxidative stress–induced hyper-activation of PARP1, and mitochondrial dysfunction associated with PD pathology. Additionally, this study also intends to investigate the alterations in neurobehavioral and biochemical parameters associated with PD pathology. Materials and Methods: An in silico docking study was conducted to investigate the phytochemicals found in M. oleifera (MO, drumstick plant) leaves as the potent inhibitors of PARP1. An in vivo (neurobehavioral, biochemical, and western blot) study was conducted to assess the neuroprotective effect of MOE on the MPTP-induced Parkinsonian mouse model. Results: The results of in silico study showed that the phytochemicals found in MO leaves could be a potent inhibitor of PAPR1. The in vivo study results showed that MOE significantly ameliorated MPTP-induced neurobehavioral and biochemical deficits. MPTP-induced mitochondrial enzyme-complex deficits were found to be restored in MOE-treated mice. Additionally, the result obtained in the western blot analysis showed that MOE significantly restored the levels of tyrosine hydroxylase in MPTP-intoxicated mice. MOE enhanced the expression of the anti-apoptotic factor (Bcl-2) and suppressed the expression of pro-apoptotic factors (Bax and caspase-3). Additionally, the enhanced levels of α-synuclein and PARP1 were significantly suppressed by MOE. Conclusion: Our findings suggest that MOE may possess pharmacological properties that inhibit neuronal damage in MPTP-intoxicated mice. Thus, MOE could be used as a therapeutic agent that can protect dopaminergic neurons from PARP1-induced neuronal damage.
Comparison of intraocular lens tilt after capsular sutured scleral fixation with capsular segments versus uneventful cataract surgery
Authors: Chang-Sotomayor Meilin , Gϋell José L. , de Rojas Silva Ma Victoria , Corretger Xavier , Bandeira Francisco , Mendez-Mourelle Andrea , Veillet Lorea Zurutuza , Adán Alfredo , Figueras-Roca Marc 
Published: January 2024

Purpose To evaluate and compare intraocular lens (IOL) tilt between uneventful phacoemulsification with in-the-bag IOL implantation and sutured scleral fixation (SSF) of the lens bag with a capsular tension segment (type 6 D / Morcher) using a Sheimpflug camera. Setting Clinical Practice, Hospital. Barcelona and A Coruña, Spain. Design Retrospective, comparative multicenter study. Methods IOL tilt was compared between patients who underwent sutured scleral fixation with a capsular tension segment in a single eye (SSF group, n = 15) with patients who underwent uneventful IOL implantation (control group, n = 12) that were matched by biometric measurements. Post-operative refractive accuracy of biometric formulas by means of mean absolute error (MAE) was also reported. All patients underwent a general ophthalmic evaluation, anterior segment photography, and postoperative optical biometry (Zeiss IOLMaster® 500). In addition, IOL tilt was measured with a Scheimpflug camera (Pentacam R, Oculus Optikgerate Gmbh). Results Mean vertical tilt was similar in both groups (2.20+/-2.47° SSF vs 1.97 +/- 1.79° control; p = 0.836) but mean horizontal tilt tended to higher values in the SSF series (2.09 +/- 2.74° vs 0.94 +/- 1.17°; p = 0.139). Considering post-operative refractive error in diopters by MAE calculations, there was an underestimation of IOL power in the SSF group which was only statistically significant for Barrett Universal II (1.07 vs 0.32; p = 0.028) and Hill-RBF (0.95 vs 0.26; p = 0.024) formulas, but not for SRK/T (0.99 vs 0.42; p = 0.285) and Kane (0.96 vs 0.33; p = 0.083). Conclusion Sutured scleral fixation of capsular tension segments in the presence of zonular instability does not seem to induce clinically significant IOL tilt compared to uneventful cataract extraction cases.