bluuebunny/crossref_metadata_2025_split huggingface dataset:
Within‐island diversification in the land snail genus Formosana (Gastropoda, Clausiliidae) in Taiwan
Authors: Hwang Chung‐Chi , Ger Mang‐Jye , Wu Shu‐Ping 
Published: July 2022

AbstractThe morphology‐based species delimitation of the land snail genus Formosana (Clausiliidae) was questioned, due to the high intraspecific variability and interspecific similarity of morphological characters. The systematics of Formosana from Taiwan are revised using molecular, morphological, and anatomical data. Phylogenies were constructed based on four mitochondrial and nuclear markers, by means of maximum likelihood and Bayesian inference analyses. Twelve valid and endemic species and subspecies were recognised from Taiwan, six of which are newly described herein: Formosana nanaoensis sp. n., Formosana hsuehshanensis sp. n., Formosana lilongshanensis sp. n., Formosana katipulensis sp. n., Formosana kaluluanensis sp. n., and Formosana tianchihensis sp. n. In addition, three nominal species are maintained as synonyms of earlier described species. A congener from China is transferred to the genus Formosanella as a new combination, Formosanella friniana com. n. The variability in morphological characteristics, and resulting difficulties for their taxonomic implication are critically discussed. Divergence time estimation and ancestral range reconstructions indicate that the Taiwanese Formosana most likely colonised in eastern Taiwan, approximately 4.7 million years ago in the Early Pliocene, and then differentiated into four major clades. The speciation events mainly occurred during the Late Pliocene and the Early Pleistocene. The biogeography and diversification of Formosana in Taiwan are discussed, in light of the concept of palaeoislands.
’We are trying to live in a normal way, but nothing is normal about us anymore…’: a qualitative study of women’s lived experiences of healthcare in opposition-controlled areas of Syria
Authors: Alhaffar Mervat , Hamid Aseel , Douedari Yazan , Howard Natasha 
Published: July 2022

IntroductionThe Syrian conflict, which has included mass killings, displacement, infrastructure destruction and illegal targeting of health facilities and staff mainly by the Syrian government and allies, is in its 10th year. This study explored the lived experiences of women within healthcare, both as health workers and service users, in Syrian opposition-controlled areas (OCAs).MethodsWe chose a qualitative study design, with 20 in-depth interviews conducted remotely over WhatsApp and Messenger with purposively sampled Syrian women (ie, 15 health workers, 5 service users). We analysed data using interpretative phenomenological analysis.ResultsAnxiety, fear and horror affected women’s everyday work and wellness. Excess workload and insecurity were major challenges for women health workers, who also had household and caring responsibilities. Coping mechanisms included: (1) normalising death; (2) acceptance of God’s will; and (3) focusing on controllable issues such as health services provision while accepting the reality of insecurity and death. Conflict contributed to changing social norms and expectations, and women became key actors in healthcare provision, though this did not translate directly into greater decision-making authority. Structural biases (eg, lack of maternity leave) and gender-based violence (eg, increased harassment and child marriage) inordinately affected women.ConclusionThis is a first effort to amplify women’s voices in health policy and systems research on the Syrian conflict. Women have become key healthcare providers in OCAs but remain under-represented in decision making. While the conflict-related social transformation, increasing the role of—and demand for—women health workers could be viewed positively for women’s empowerment, the reality is complex and long-term implications are unclear.
Salt restriction and risk of adverse outcomes in heart failure with preserved ejection fraction
Authors: Li Jiayong , Zhen Zhe , Huang Peisen , Dong Yu-Gang , Liu Chen , Liang Weihao 
Published: July 2022

BackgroundThe optimal salt restriction in patients with heart failure (HF), especially patients with heart failure with preserved ejection fraction (HFpEF), remains controversial.ObjectiveTo investigate the associations of cooking salt restriction with risks of clinical outcomes in patients with HFpEF.MethodsCox proportional hazards model and subdistribution hazards model were used in this secondary analysis in 1713 participants with HFpEF from the Americas in the TOPCAT trial. Cooking salt score was the sum of self-reported salt added during homemade food preparation. The primary endpoint was a composite of cardiovascular death, HF hospitalisation and aborted cardiac arrest, and secondary outcomes were all-cause death, cardiovascular death and HF hospitalisation.ResultsCompared with patients with cooking salt score 0, patients with cooking salt score >0 had significantly lower risks of the primary endpoint (HR=0.760, 95% CI 0.638 to 0.906, p=0.002) and HF hospitalisation (HR=0.737, 95% CI 0.603 to 0.900, p=0.003), but not all-cause (HR=0.838, 95% CI 0.684 to 1.027, p=0.088) or cardiovascular death (HR=0.782, 95% CI 0.598 to 1.020, p=0.071). Sensitivity analyses using propensity score matching baseline characteristics and in patients who prepared meals mostly at home yielded similar results. Subgroup analysis suggested that the association between overstrict salt restriction and poor outcomes was more predominant in patients aged ≤70 years and of non-white race.ConclusionOverstrict cooking salt intake restriction was associated with worse prognosis in patients with HFpEF, and the association seemed to be more predominant in younger and non-white patients. Clinicians should be prudent when giving salt restriction advice to patients with HFpEF.
Preinduced reovirus-specific T-cell immunity enhances the anticancer efficacy of reovirus therapy
Authors: Groeneveldt Christianne , Kinderman Priscilla , van Stigt Thans Jordi J C , Labrie Camilla , Griffioen Lisa , Sluijter Marjolein , van den Wollenberg Diana J M , Hoeben Rob C , den Haan Joke M M , van der Burg Sjoerd H , van Hall Thorbald , van Montfoort Nadine 
Published: July 2022

BackgroundMany solid tumors do not respond to immunotherapy due to their immunologically cold tumor microenvironment (TME). We and others found that oncolytic viruses (OVs), including reovirus type 3 Dearing, can enhance the efficacy of immunotherapy by recruiting CD8+T cells to the TME. A significant part of the incoming CD8+T cells is directed toward reovirus itself, which may be detrimental to the efficacy of OVs. However, here we aim to exploit these incoming virus-specific T cells as anticancer effector cells.MethodsWe performed an in-depth characterization of the reovirus-induced T-cell response in immune-competent mice bearing pancreatic KPC3 tumors. The immunodominant CD8+T-cell epitope of reovirus was identified using epitope prediction algorithms and peptide arrays, and the quantity and quality of reovirus-specific T cells after reovirus administration were assessed using high-dimensional flow cytometry. A synthetic long peptide (SLP)-based vaccination strategy was designed to enhance the intratumoral frequency of reovirus-specific CD8+T cells.ResultsReovirus administration did not induce tumor-specific T cells but rather induced high frequencies of reovirus-specific CD8+T cells directed to the immunodominant epitope. Priming of reovirus-specific T cells required a low-frequent population of cross-presenting dendritic cells which was absent inBatf3-/-mice. While intratumoral and intravenous reovirus administration induced equal systemic frequencies of reovirus-specific T cells, reovirus-specific T cells were highly enriched in the TME exclusively after intratumoral administration. Here, they displayed characteristics of potent effector cells with high expression of KLRG1, suggesting they may be responsive against local reovirus-infected cells. To exploit these reovirus-specific T cells as anticancer effector cells, we designed an SLP-based vaccination strategy to induce a strong T-cell response before virotherapy. These high frequencies of circulating reovirus-specific T cells were reactivated on intratumoral reovirus administration and significantly delayed tumor growth.ConclusionsThese findings provide proof of concept that OV-specific T cells, despite not being tumor-specific, can be exploited as potent effector cells for anticancer treatment when primed before virotherapy. This is an attractive strategy for low-immunogenic tumors lacking tumor-specific T cells.
Cost-effectiveness of motivational counselling and text reminders in patients with rheumatoid arthritis: results based on a randomised clinical trial
Authors: Sørensen Jan , Esbensen Bente Appel , Aadahl Mette , Hetland Merete Lund , Thomsen Tanja 
Published: July 2022

ObjectiveThe aim of this study was to evaluate the cost-effectiveness of an individually tailored intervention consisting of motivational counselling and text message reminders to reduce sedentary behaviour in comparison with usual lifestyle in patients with rheumatoid arthritis (RA).MethodsRA patients (n=150) were randomised to the intervention or control group. Costs of the intervention and healthcare utilisation during a 22-month follow-up period were reported. Outcomes were objectively measured as 24 hours/7 days sitting time and self-reported Health Assessment Questionnaire (HAQ) and EQ-5D scores at baseline, and 16 weeks, 10 and 22 months after baseline. Cost-effectiveness was reported as incremental cost-effectiveness ratios and statistical uncertainty presented as cost-effectiveness acceptability curves.ResultsThe intervention cost was estimated at €387 per participant. The mean incremental 22-month healthcare cost was €−1165 (95% bootstrap CI −5613 to 3283). An incremental 20%-point of the participants (CI 10.4% to 29.6%) reduced their daily sitting time more than 50 min and 36%-point reported better HAQ scores (change>0.22). The time-weighted health utilities (quality-adjusted life years (QALYs)) increased by 0.10 (CI 0.02 to 0.18) and 0.11 (CI 0.04 to 0.19) for EQ-5D index and EQ-VAS, respectively. The intervention dominated usual lifestyle by offering better outcomes and lower costs. With a threshold value of €30 000/QALY the intervention has a probability of 95% of being cost-effective.ConclusionThis protocolised cost-effectiveness analysis showed that an individually tailored intervention aimed at reducing sedentary behaviour in patients with RA is improving participants’ 22-month health status and reducing healthcare costs. These results suggest that the intervention should be implemented in routine rheumatology care.Trial registration numberNCT01969604.Trial registration number
Femtoscopic study on $$DD^*$$ and $$D\bar{D}^*$$ interactions for $$T_{cc}$$ and X(3872)
Authors: Kamiya Yuki , Hyodo Tetsuo , Ohnishi Akira 
Published: July 2022

AbstractWe investigate $$DD^*$$

D

D
∗

and $$D\bar{D}^*$$

D

D

¯

∗

momentum correlations in high-energy collisions to elucidate the nature of $$T_{cc}$$

T

cc

and X(3872) exotic hadrons. Single range Gaussian potentials with the channel couplings to the isospin partners are constructed based on the empirical data within the pure hadronic-molecule picture. The momentum correlation functions of the $$D^0D^{*+}$$

D
0

D

∗
+

, $$D^+D^{*0}$$

D
+

D

∗
0

, $$D^0\bar{D}^{*0}$$

D
0

D

¯

∗
0

, and $$D^+D^{*-}$$

D
+

D

∗
-

pairs are computed with including the coupled-channel effects. We discuss how the nature of the exotic states are reflected in the behaviors of the correlation results.
EFFECTS OF CERVICAL TRACTION AND INFRARED THERAPY ON PAIN INTENSITY AND NECK DISABILITY INDEX AMONG PEOPLE WITH CERVICAL SPONDYLOSIS: A CROSS-OVER COHORT STUDY
Authors: Igwe Augustine Asiduba , Onyeso Ogochukwu Kelechi , Ezema Charles Ikechukwu , Eyichukwu Gabriel Okey , Ejim Emmanuel Chukwudi , Egwuonwu Victor A. , Onwujekwe Obinna , Amaeze Amaeze Augustine , Okoye Goddy Chuba 
Published: July 2022

Objective: To investigate the effects of six-week cervical traction and infrared therapy on neck pain intensity (PI) and neck disability index (NDI) among individuals with cervical spondylosis. Methods: This study was a non-randomized cross-over cohort design. A total of 40 participants (men=20, and women=20) who were purposively selected, received a six-week infrared therapy, observed a one-week washout period, and then six-week concurrent infrared therapy and cervical traction. The PI and NDI were measured at baseline, after infrared therapy, the washout period, and infrared plus cervical traction. Data were analyzed using repeated-measures analysis of variance (RM ANOVA), Friedman’s ANOVA, independent samples t-test, and Kendall’s tau correlation test. Result: The mean age of the participants was 40±8.60 years. Infrared therapy plus cervical traction significantly reduced PI: [Formula: see text]2(3)=102.06, [Formula: see text], and NDI: F (1, 39) = 222.56, [Formula: see text], relative to infrared therapy alone. Specifically, the minimum clinically important difference (MCID) for PI was 2.2, while infrared alone reduced the PI by 1.0 (Z = 4.633, [Formula: see text]), infrared therapy plus cervical traction reduced PI by 6.0 (Z = 7.405, [Formula: see text]). The MCID for NDI was 8.50, while infrared alone reduced the NDI by 1.05 (t = 30.087, [Formula: see text]), infrared therapy plus cervical traction reduced NDI by 15.83 ([Formula: see text], [Formula: see text]). Conclusion: Concurrent infrared and cervical traction significantly reduced PI and NDI among patients with cervical spondylosis more than lone infrared therapy.
DISTAL TIBIA SOLITARY OSTEOCHONDROMA-A CASE SERIES
Authors: Bishnoi Ramniwas , Jain Hemant , Bharwani Nandlal , Chouhan Jayesh , Choudhary Pradeep , Bhati Mahesh 
Published: July 2022

Introduction: Distal tibia involvement is very rare and it merely accounts for around 4% of all the excised lesions. (Mirra, 1989) Distal tibia osteochondromas mainly present pain, deformity like varus/valgus around ankle joint, pathologic fractures of surrounding structures and for the above-mentioned problems, surgical excision has to be considered as a possible option. (Ismail et al., 2008). Methods: We conducted a prospective study from 1st June 2018 to 1st June 2021 including five patients (4 males and 1 female) with distal tibia osteochondroma. In our study, surgical excision was performed in all the cases. Pre-operative and at final follow-up ‘AOFAS-AHFS score’ and ‘VAS score’ were evaluated. Results: All five patients had good functional outcome at final follow-up, mean AOFAS-AHFS score improved from 61.2±5.4 to 85±3.39, and mean VAS score improved from 7.2±0.83 to 0.8±0.44 at final follow-up and found no difficulty in daily routine activities. All patients had complete ROM at final follow-up. Conclusion: Distal tibia osteochondroma has good functional outcome and less complications, if managed properly.
Do Chest Compresses with Mustard or Ginger Affect Warmth Regulation in Healthy Adults? A Randomized Controlled Trial
Authors: Vagedes Jan , Kuderer Silja , Vagedes Katrin , Szőke Henrik , Kohl Matthias , Joos Stefanie , Beissner Florian , Wolf Ursula 
Published: July 2022

Background. Chest compresses with mustard (MU) or ginger (GI) are a complementary treatment option for respiratory tract infections. However, little is known about their specific thermogenic qualities. This study examines the short-term effects of MU, GI, and chest compresses with warm water only (WA) on measurable and self-perceived body warmth in healthy adults. Methods. This was a single-center, randomized controlled trial with cross-over design (WA versus MU versus GI). 18 participants (23.7 ± 3.4 years; 66.7% female) received MU, GI, and WA in a random order on three different days with a mean washout period of 13.9 days. Chest compresses were applied to the thoracic back for a maximum of 20 minutes. The primary outcome measure was skin temperature of the posterior trunk (measured by infrared thermography) immediately following removal of the compresses (t1). Secondary outcome measures included skin temperature of the posterior trunk 10 minutes later (t2) and several parameters of self-perceived warmth at t1 and t2 (assessed with the Herdecke Warmth Perception Questionnaire). Results. Skin temperature of the posterior trunk was significantly higher with MU compared to WA and GI at t1 (

p

< 0.001 for both, primary outcome measure) and t2 (WA versus MU:

p
=
0.04

, MU versus GI:

p
<
0.01

). Self-perceived warmth of the posterior trunk was higher with MU and GI compared to WA at t1 (1.40 ≥ d ≥ 1.79) and remained higher with GI at t2 (WA versus GI: d = 0.74). The overall warmth perception increased significantly with GI (d = 0.69), tended to increase with MU (d = 0.54), and did not change with WA (d = 0.36) between t0 and t1. Conclusions. Different effects on warmth regulation were observed when ginger and mustard were applied as chest compresses. Both substances induced self-perceived warming of the posterior trunk, but measurable skin temperature increased only with MU. Further research is needed to examine the duration of these thermogenic effects and how chest compresses with ginger or mustard might be incorporated into practice to influence clinical outcomes in respiratory tract infections.
Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach
Authors: Roeker Lindsey E. , Feldman Tatyana A. , Soumerai Jacob D. , Falco Victoria , Panton Gail , Dorsey Colleen , Zelenetz Andrew D. , Falchi Lorenzo , Park Jae H. , Straus David J. , Pena Velasquez Camila , Lebowitz Sonia , Fox Yehudit , Battiato Kristen , Laudati Carissa , Thompson Meghan C. , McCarthy Elizabeth , Kdiry Sabrina , Martignetti Rosalba , Turpuseema Teja , Purdom Michelle , Paskalis Dana , Miskin Hari P. , Sportelli Peter , Leslie Lori A. , Mato Anthony R. 
Published: July 2022

Abstract

Purpose:
Ibrutinib has transformed the management of chronic lymphocytic leukemia (CLL), though its use is limited by toxicity and resistance. In this study, we utilized an “add on” approach for patients who had been treated with ibrutinib in the front-line or relapsed/refractory settings with detectable MRD. Umbralisib and ublituximab (U2) were added on to ibrutinib, patients were treated until achieving undetectable-MRD (U-MRD), and then they entered a period of treatment-free observation (TFO).

Patients and Methods:
Patients were eligible if they received ibrutinib in any line of therapy for at least 6 months and had detectable MRD (flow cytometry, &lt;1 cell in 10–4 cutoff for U-MRD). U2 was added to ibrutinib, and patients were monitored serially for MRD. Once U-MRD was achieved or a total of 24 cycles were administered, patients entered a period of TFO. The primary study objective was rate of U-MRD. Secondary endpoints included safety and durability of clinical benefit after treatment discontinuation.

Results:
Twenty-eight patients were enrolled of whom 27 were evaluable for efficacy. Patients received ibrutinib for a median of 21 months (range 7–67) prior to study enrollment. Fourteen patients (52%) have achieved U-MRD per protocol whereas 78% had at least one U-MRD evaluation. Seventeen patients (63%) have entered TFO after a median of 6.4 months on triplet therapy. Progression-free survival at 12 months was estimated at 95%. Grade ≥3 adverse events were hypertension 7%, diarrhea 4%, and increased ALT/AST 4%.

Conclusions:
This triplet approach utilizes the addition of U2 to ibrutinib as an MRD-driven time-limited therapy. This therapy was well tolerated and effective. TFO following this therapy appears durable in ongoing follow-up.
Intronic Cis-Element DR8 in hTERT Is Bound by Splicing Factor SF3B4 and Regulates hTERT Splicing in Non–Small Cell Lung Cancer
Authors: Slusher Aaron L. , Kim Jeongjin J. , Ribick Mark , Pollens-Voigt Jesse , Bankhead Armand , Palmbos Phillip L. , Ludlow Andrew T. 
Published: July 2022

Abstract

Splicing of the hTERT gene to produce the full-length (FL) transcript is necessary for telomerase enzyme activity and telomere-dependent cellular immortality in the majority of human tumors, including non–small cell lung cancer (NSCLC) cells. The molecular machinery to splice hTERT to the FL isoform remains mostly unknown. Previously, we reported that an intron 8 cis-element termed “direct repeat 8” (DR8) promotes FL hTERT splicing, telomerase, and telomere length maintenance when bound by NOVA1 and PTBP1 in NSCLC cells. However, some NSCLC cells and patient tumor samples lack NOVA1 expression. This leaves a gap in knowledge about the splicing factors and cis-elements that promote telomerase in the NOVA1-negative context. We report that DR8 regulates FL hTERT splicing in the NOVA1-negative and -positive lung cancer contexts. We identified splicing factor 3b subunit 4 (SF3B4) as an RNA trans-factor whose expression is increased in lung adenocarcinoma (LUAD) tumors compared with adjacent normal tissue and predicts poor LUAD patient survival. In contrast to normal lung epithelial cells, which continued to grow with partial reductions of SF3B4 protein, SF3B4 knockdown reduced hTERT splicing, telomerase activity, telomere length, and cell growth in lung cancer cells. SF3B4 was also demonstrated to bind the DR8 region of hTERT pre-mRNA in both NOVA1-negative and -positive NSCLC cells. These findings provide evidence that DR8 is a critical binding hub for trans-factors to regulate FL hTERT splicing in NSCLC cells. These studies help define mechanisms of gene regulation important to the generation of telomerase activity during carcinogenesis.

Implications:
Manipulation of a core spliceosome protein reduces telomerase/hTERT splicing in lung cancer cells and results in slowed cancer cell growth and cell death, revealing a potential therapeutic strategy.
Donor Utilization in the Recent Era: Effect of Sex, Drugs, and Increased Risk
Authors: Baran David A. , Long Ashleigh , Lansinger Justin , Copeland Jack G. , Copeland Hannah 
Published: July 2022

Background:
Heart transplantation volumes have increased in recent years, yet less than a third of donors are typically accepted for transplantation. Whether donor sex, donor drug use, or perception of increased risk affects utilization for transplantation is unclear.

Methods:
The United Network for Organ Sharing database was queried for donors from January 1, 2007, to December 31, 2017. Donor toxicology was collected when available. Multivariate analysis was conducted to examine correlations with donor utilization.

Results:
Between January 1, 2007, and December 31, 2017, there were 87 816 heart donors aged ≥15 years. The mean age was 42.7±15.8 years, and 24 831 donors (28.3%) were utilized for heart transplantation. Subsequent analyses focused on donors between 15 and 39 years old.
The strongest associations with donor acceptance were for male donor sex, blood type, hepatitis C antibody, donor age, left ventricular hypertrophy, and history of donor drug use. After removing hepatitis C, Public Health Service Increased Risk was identified as a strong negative predictor. Most positive drug toxicology results were associated with donor nonuse except for donors between 15 and 19 years of age. Exceptions included alcohol, marijuana, and cocaine. Opiates were associated with less utilization at all donor ages. The Public Health Service Increased Risk status was associated with significantly less utilization in all age groups except 15- to 19-year-old donors.

Conclusions:
While male donors were preferentially utilized, donors with drug use or those deemed Public Health Service Increased Risk were significantly less utilized for heart transplantation. Further consideration of such donors would be appropriate particularly as the demand for transplantation continues to increase.