bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of Anatomic Bony Landmark Localization of the ACL Femoral Footprint Using 3D MRI
Authors: Sivakumaran Thiru , Jaffer Rehana , Marwan Yousef , Hart Adam , Radu Arnold , Burman Mark , Martineau Paul A. , Powell Tom 
Published: October 2021

Background: Nonanatomic placement of anterior cruciate ligament (ACL) grafts is a leading cause of ACL graft failure. Three-dimensional (3D) magnetic resonance imaging (MRI) femoral footprint localization could enhance planning for an ACL graft's position. Purpose: To determine the intra- and interobserver reliability of measurements of the ACL femoral footprint position and size obtained from 3D MRI scans. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 41 patients with complete ACL tears were recruited between November 2014 and May 2016. Preoperatively, a coronal-oblique proton-density fast spin echo 3D acquisition of the contralateral uninjured knee was obtained along the plane of the ACL using a 1.5T MRI scanner. ACL footprint parameters were obtained independently by 2 musculoskeletal radiologists (observers A and B). The distal and anterior positions of the center of the footprint were measured relative to the apex of the deep cartilage at the posteromedial aspect of the lateral femoral condyle, and the surface area of the ACL femoral footprint was approximated from multiplanar reformatted images. After 1 month, the measurements were repeated. Intraclass correlation coefficients (ICCs) were calculated to assess for intra- and interobserver reliability. Bland-Altman plots were produced to screen for potential systematic bias in measurement and to calculate limits of agreement. Results: The ICCs for intraobserver reliability of the ACL femoral distal and anterior footprint coordinates were 0.75 and 0.78, respectively, for observer A. For observer B, they were 0.75 and 0.74, respectively. The ICCs for interobserver reliability were 0.75 and 0.85 for the distal and anterior coordinates, respectively. Bland-Altman plots demonstrated no significant systematic bias. For surface area measurements, the intraobserver ICCs were 0.37 and 0.62 for observers A and B, respectively. The interobserver reliability was 0.60. Observer B consistently measured the footprints as slightly larger versus observer A (1.19 ± 0.27 vs 1 ± 0.22 cm2, respectively; P < .001). Conclusion: Locating the center of the anatomic footprint of the ACL with 3D MRI showed substantial intra- and interobserver agreement. Interobserver agreement for the femoral footprint surface area was fair to moderate.
The Effect of a Portable Electrical Muscle Stimulation on Brain-Derived Neurotrophic Factor in Elderly People: Three Case Studies
Authors: Nishikawa Yuichi , Watanabe Kohei , Kawade Shuhei , Maeda Noriaki , Maruyama Hirofumi 
Published: October 2021

Brain-derived neurotrophic factor (BDNF), which plays an important role in cognitive and nerve function, is released from skeletal muscle cells into the blood by muscle contractions and/or electrical muscle stimulation (EMS). However, the influence of EMS administered by a portable device on BDNF is unclear. The purpose of this case report was to quantify the influence of EMS administered by a portable device on BDNF and physical function. Three elderly people (age, 69.7 ± 1.5 years) were included in the present study. The participants used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min for 5 days/week). To determine the effects of EMS, the following parameters were assessed at baseline, 8 weeks, and 12 weeks (follow-up): knee extensor strength, muscle mass of the lower limb, Berg balance score, and blood BDNF level. All outcomes improved after the EMS intervention, but the improvements did not persist for 12 weeks. These findings suggest that portable EMS is potentially useful for improving the blood BDNF level and physical function.
Reliability, validity, and responsiveness to change of the Patient-Reported Outcomes Measurement Information System self-efficacy for managing chronic conditions measure in systemic sclerosis
Authors: Murphy Susan L , Berrocal Veronica J , Poole Janet L , Khanna Dinesh 
Published: October 2021

Objective: The aim of this study is to examine validity, reliability, and responsiveness to change of Patient-Reported Outcomes Measurement Information System Self-Efficacy for Managing Chronic Conditions in persons with systemic sclerosis. Methods: We conducted a post hoc analysis of the Patient-Reported Outcomes Measurement Information System Self-Efficacy measure and other quality-of-life measures from systemic sclerosis participants from a 16-week randomized control trial. The trial compared an Internet-based self-management program to a control condition where participants were provided an educational book. All participants completed outcome measures at baseline and following the 16-week trial period. Results: The mean age of participants was 53.7 years, 91% were female and systemic sclerosis subtype included 44.9% limited/sine and 43.1% diffuse; mean disease duration was 9.0 years. All self-efficacy subscales (Managing Emotions, Symptoms, Daily Activities, Social Interactions, and Medications/Treatment) demonstrated good internal consistency (.92–.96). All subscales showed statistically significant correlations with other validated measures of depressive symptoms and quality of life (.20–.86) but were not associated with satisfaction nor with appearance. The subscales appropriately discriminated between those with and without depressive symptoms and demonstrated responsiveness to change over the 16-week period for those who had a corresponding increase in reported quality of life. Conclusion: The Patient-Reported Outcomes Measurement Information System Self-Efficacy measure is valid, reliable, and responsive to change for persons with systemic sclerosis.
Alloreactive T cells deficient of the short-chain fatty acid receptor GPR109A induce less graft-versus-host disease
Authors: Docampo Melissa D. , da Silva Marina B. , Lazrak Amina , Nichols Katherine B. , Lieberman Sophia R. , Slingerland Ann E. , Armijo Gabriel K. , Shono Yusuke , Nguyen Chi , Monette Sebastien , Dwomoh Emmanuel , Lee Nicole , Geary Clair D. , Perobelli Suelen M. , Smith Melody , Markey Kate A. , Vardhana Santosha A. , Kousa Anastasia I. , Zamir Eli , Greenfield Itamar , Sun Joseph C. , Cross Justin R. , Peled Jonathan U. , Jenq Robert R. , Stein-Thoeringer Christoph K. , van den Brink Marcel R. M. 
Published: October 2021

Abstract
The intestinal microbiota is essential for the fermentation of dietary fiber into short-chain fatty acids (SCFA) such as butyrate, acetate, and propionate. SCFAs can bind to the G-protein-coupled receptors GPR43 and GPR109A (HCAR2), with varying affinities to promote cellular effects in metabolism or changes in immune function. We explored the role of GPR109A as the main receptor for butyrate in mouse models of allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD). Deletion of GPR109A in allo-HCT recipients did not affect GVHD, but transplantation of T cells from GPR109A knockout (KO) (Gpr109a−/−) mice into allo-HCT recipient mice significantly reduced GVHD morbidity and mortality compared with recipients of wild-type (WT) T cells. Recipients of Gpr109a−/− T cells exhibited less GVHD-associated target organ pathology and decreased proliferation and homing of alloreactive T cells to target tissues. Although Gpr109a−/− T cells did not exhibit immune deficits at a steady state, following allo-activation, Gpr109a−/− T cells underwent increased apoptosis and were impaired mitochondrial oxidative phosphorylation, which was reversible through antioxidant treatment with N-acetylcysteine (NAC). In conclusion, we found that GPR109A expression by allo-activated T cells is essential for metabolic homeostasis and expansion, which are necessary features to induce GVHD after allo-HCT.
Autophagy in mesenchymal progenitors protects mice against bone marrow failure after severe intermittent stress
Authors: Landspersky Theresa , Saçma Mehmet , Rivière Jennifer , Hecker Judith S. , Hettler Franziska , Hameister Erik , Brandstetter Katharina , Istvánffy Rouzanna , Romero Marquez Sandra , Ludwig Romina , Götz Marilena , Buck Michèle , Wolf Martin , Schiemann Matthias , Ruland Jürgen , Strunk Dirk , Shimamura Akiko , Myers Kasiani , Yamaguchi Terry P. , Kieslinger Matthias , Leonhardt Heinrich , Bassermann Florian , Götze Katharina S. , Geiger Hartmut , Schreck Christina , Oostendorp Robert A. J. 
Published: October 2021

Abstract
The cellular mechanisms required to ensure homeostasis of the hematopoietic niche and the ability of this niche to support hematopoiesis upon stress remain elusive. We here identify Wnt5a in Osterix+ mesenchymal progenitor and stem cells (MSPCs) as a critical factor for niche-dependent hematopoiesis. Mice lacking Wnt5a in MSPCs suffer from stress-related bone marrow (BM) failure and increased mortality. Niche cells devoid of Wnt5a show defective actin stress fiber orientation due to an elevated activity of the small GTPase CDC42. This results in incorrect positioning of autophagosomes and lysosomes, thus reducing autophagy and increasing oxidative stress. In MSPCs from patients from BM failure states which share features of peripheral cytopenia and hypocellular BM, we find similar defects in actin stress fiber orientation, reduced and incorrect colocalization of autophagosomes and lysosomes, and CDC42 activation. Strikingly, a short pharmacological intervention to attenuate elevated CDC42 activation in vivo in mice prevents defective actin-anchored autophagy in MSPCs, salvages hematopoiesis and protects against lethal cytopenia upon stress. In summary, our study identifies Wnt5a as a restriction factor for niche homeostasis by affecting CDC42-regulated actin stress-fiber orientation and autophagy upon stress. Our data further imply a critical role for autophagy in MSPCs for adequate support of hematopoiesis by the niche upon stress and in human diseases characterized by peripheral cytopenias and hypocellular BM.
A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas
Authors: Moskowitz Alison J. , Ghione Paola , Jacobsen Eric , Ruan Jia , Schatz Jonathan H. , Noor Sarah , Myskowski Patricia , Vardhana Santosha , Ganesan Nivetha , Hancock Helen , Davey Theresa , Perez Leslie , Ryu Sunyoung , Santarosa Alayna , Dowd Jack , Obadi Obadi , Pomerantz Lauren , Yi Nancy , Sohail Samia , Galasso Natasha , Neuman Rachel , Liotta Brielle , Blouin William , Baik Jeeyeon , Geyer Mark B. , Noy Ariela , Straus David , Kumar Priyadarshini , Dogan Ahmet , Hollmann Travis , Drill Esther , Rademaker Jurgen , Schoder Heiko , Inghirami Giorgio , Weinstock David M. , Horwitz Steven M. 
Published: October 2021

Abstract
Signaling through JAK1 and/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1/2 inhibitor ruxolitinib for patients with relapsed/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7). Patients enrolled onto 1 of 3 biomarker-defined cohorts: (1) activating JAK and/or STAT mutations, (2) ≥30% pSTAT3 expression among tumor cells by immunohistochemistry, or (3) neither or insufficient tissue to assess. Patients received ruxolitinib 20 mg PO twice daily until progression and were assessed for response after cycles 2 and 5 and every 3 cycles thereafter. The primary endpoint was clinical benefit rate (CBR), defined as the combination of complete response, partial response (PR), and stable disease lasting at least 6 months. Only 1 of 7 patients with MF had CBR (ongoing PR &gt; 18 months). CBR among the PTCL cases (n = 45) in cohorts 1, 2, and 3 were 53%, 45%, and 13% (cohorts 1 & 2 vs 3, P = .02), respectively. Eight patients had CBR &gt; 12 months (5 ongoing), including 4 of 5 patients with T-cell large granular lymphocytic leukemia. In an exploratory analysis using multiplex immunofluorescence, expression of phosphorylated S6, a marker of PI3 kinase or mitogen-activated protein kinase activation, in &lt;25% of tumor cells was associated with response to ruxolitinib (P = .05). Our findings indicate that ruxolitinib is active across various PTCL subtypes and support a precision therapy approach to JAK/STAT inhibition in patients with PTCL. This trial was registered at www.clincialtrials.gov as #NCT02974647.
Multiple myeloma cells induce lipolysis in adipocytes and uptake fatty acids through fatty acid transporter proteins
Authors: Panaroni Cristina , Fulzele Keertik , Mori Tomoaki , Siu Ka Tat , Onyewadume Chukwuamaka , Maebius Allison , Raje Noopur 
Published: October 2021

Abstract
Adipocytes occupy 70% of the cellular volume within the bone marrow (BM) wherein multiple myeloma (MM) originates and resides. However, the nature of the interaction between MM cells and adipocytes remains unclear. Cancer-associated adipocytes support tumor cells through various mechanisms, including metabolic reprogramming of cancer cells. We hypothesized that metabolic interactions mediate the dependence of MM cells on BM adipocytes. Here we show that BM aspirates from precursor states of MM, including monoclonal gammopathy of undetermined significance and smoldering MM, exhibit significant upregulation of adipogenic commitment compared with healthy donors. In vitro coculture assays revealed an adipocyte-induced increase in MM cell proliferation in monoclonal gammopathy of undetermined significance/smoldering MM compared with newly diagnosed MM. Using murine MM cell/BM adipocyte coculture assays, we describe MM-induced lipolysis in adipocytes via activation of the lipolysis pathway. Upregulation of fatty acid transporters 1 and 4 on MM cells mediated the uptake of secreted free fatty acids (FFAs) by adjacent MM cells. The effect of FFAs on MM cells was dose dependent and revealed increased proliferation at lower concentrations vs induction of lipotoxicity at higher concentrations. Lipotoxicity occurred via the ferroptosis pathway. Exogenous treatment with arachidonic acid, a very-long-chain FFA, in a murine plasmacytoma model displayed a reduction in tumor burden. Taken together, our data reveal a novel pathway involving MM cell–induced lipolysis in BM adipocytes and suggest prevention of FFA uptake by MM cells as a potential target for myeloma therapeutics.
Co-structure analysis and genetic associations reveal insights into pinworms (Trypanoxyuris) and primates (Alouatta palliata) microevolutionary dynamics
Authors: Solórzano-García Brenda , Vázquez-Domínguez Ella , Pérez-Ponce de León Gerardo , Piñero Daniel 
Published: October 2021

AbstractBackgroundIn parasitism arm race processes and red queen dynamics between host and parasites reciprocally mold many aspects of their genetics and evolution. We performed a parallel assessment of population genetics and demography of two species of pinworms with different degrees of host specificity (Trypanoxyuris multilabiatus, species-specific; andT. minutus,genus-specific) and their host, the mantled howler monkey (Alouatta palliata), based on mitochondrial DNA sequences and microsatellite loci (these only for the host). Given that pinworms and primates have a close co-evolutionary history, covariation in several genetic aspects of their populations is expected.ResultsMitochondrial DNA revealed two genetic clusters (West and East) in both pinworm species and howler monkeys, although population structure and genetic differentiation were stronger in the host, while genetic diversity was higher in pinworms than howler populations. Co-divergence tests showed no congruence between host and parasite phylogenies; nonetheless, a significant correlation was found between both pinworms andA. palliatagenetic pairwise distances suggesting that the parasites’ gene flow is mediated by the host dispersal. Moreover, the parasite most infective and the host most susceptible haplotypes were also the most frequent, whereas the less divergent haplotypes tended to be either more infective (for pinworms) or more susceptible (for howlers). Finally, a positive correlation was found between pairwise p-distance of host haplotypes and that of their associated pinworm haplotypes.ConclusionThe genetic configuration of pinworm populations appears to be molded by their own demography and life history traits in conjunction with the biology and evolutionary history of their hosts, including host genetic variation, social interactions, dispersal and biogeography. Similarity in patterns of genetic structure, differentiation and diversity is higher between howler monkeys andT. multilabiatusin comparison withT. minutus, highlighting the role of host-specificity in coevolving processes.Trypanoxyuris minutusexhibits genetic specificity towards the most frequent host haplotype as well as geographic specificity. Results suggest signals of potential local adaptation in pinworms and further support the notion of correlated evolution between pinworms and their primate hosts.
A time-driven activity-based costing approach for identifying variability in costs of childbirth between and within types of delivery
Authors: Dubron Kathia , Verschaeve Mathilde , Roodhooft Filip 
Published: October 2021

Abstract
Background
Recently, time-driven activity-based costing (TDABC) is put forward as an alternative, more accurate costing method to calculate the cost of a medical treatment because it allows the assignment of costs directly to patients. The objective of this paper is the application of a time-driven activity-based method in order to estimate the cost of childbirth at a maternal department. Moreover, this study shows how this costing method can be used to outline how childbirth costs vary according to considered patient and disease characteristics. Through the use of process mapping, TDABC allows to exactly identify which activities and corresponding resources are impacted by these characteristics, leading to a more detailed understanding of childbirth cost.

Methods
A prospective cohort study design is performed in a maternity department. Process maps were developed for two types of childbirth, vaginal delivery (VD) and caesarean section (CS). Costs were obtained from the financial department and capacity cost rates were calculated accordingly.

Results
Overall, the cost of childbirth equals €1894,12 and is mainly driven by personnel costs (89,0%). Monitoring after birth is the most expensive activity on the pathway, costing €1149,70. Significant cost variations between type of delivery were found, with VD costing €1808,66 compared to €2463,98 for a CS. Prolonged clinical visit (+ 33,3 min) and monitoring (+ 775,2 min) in CS were the main contributors to this cost difference. Within each delivery type, age, parity, number of gestation weeks and education attainment were found to drive cost variations. In particular, for VD an age >  25 years, nulliparous, gestation weeks > 40 weeks and higher education attainment were associated with higher costs. Similar results were found within CS for age, parity and number of gestation weeks.

Conclusions
TDABC is a valuable approach to measure and understand the variability in costs of childbirth and its associated drivers over the full care cycle. Accordingly, these findings can inform health care providers, managers and regulators on process improvements and cost containment initiatives.
Does the use of telephone reminders to increase survey response rates affect outcome estimates? An ancillary analysis of a prospective cohort study of patients with low back pain
Authors: Udby Christina Lyngsø , Riis Allan , Thomsen Janus Laust , Rolving Nanna 
Published: October 2021

Abstract
Background
Research is often undertaken using patient-reported outcomes from questionnaires. Achieving a high response rate demands expensive and time-consuming methods like telephone reminders. However, it is unknown whether telephone reminders change outcome estimates or only affect the response rate in research of populations with low back pain (LBP). The aim is to compare baseline characteristics and the change in outcome between patients responding before and after receiving a telephone reminder.

Methods
This is an ancillary analysis of data from a prospective cohort study employing questionnaires from 812 adults with LBP lasting more than 3 months. Patients not responding to the 52-week questionnaire were sent reminder emails after two and 3 weeks and delivered postal reminders after 4 weeks. Patients still not responding were contacted by telephone, with a maximum of two attempts. Patients were categorised into three groups: 1) patients responding before a telephone reminder was performed; 2) patients responding after the telephone reminder and 3) patients not responding at all. A positive outcome was defined as a 30% improvement on the Roland Morris Disability Questionnaire after 52 weeks.

Results
A total of 695 patients (85.2%) responded. Of these, 643 patients were classified in Group 1 and 52 patients were classified in Group 2. One hundred seventeen were classified in Group 3. No differences in outcome or baseline characteristics was found. In Group 1, 41.3% had a positive outcome, and in Group 2 48.9% had a positive outcome (P = 0.297). In group 3, non-respondents were younger, more often unemployed, more often smokers, more often reported co-morbidity, and reported higher depression scores than respondents.

Conclusions
Using a telephone reminder had no consequence on outcome estimates nor were there any differences in baseline characteristics between patients who responded before or after the telephone reminder.

Trial registration
The initial trial was registered in Clinicaltrials.gov (NCT03058315).
Increasing rates of laparoscopic gastrointestinal surgery and decreasing rates of surgical site infections: an observational study in Japan from 2012–2017
Authors: Takahashi Tomoko , Nishiura Hiroshi 
Published: October 2021

Abstract
Background
Surgical site infections (SSI) are the most common healthcare-associated infection, and gastrointestinal surgery is frequently followed by a high incidence of SSI. Epidemiological analysis of the temporal trends in SSI following gastrointestinal surgery has yet to be performed in Japan. Our purpose was to descriptively investigate these trends.

Methods
Extracting national surveillance data from the Japan Nosocomial Infections Surveillance (JANIS) system, we analyzed the frequency of SSI events following gastrointestinal surgery, which consisted of seven surgical procedures, from 2012–2017. We calculated the standardized infection ratio to compute risk-adjusted SSI frequency, and used the trend test to detect time-dependent changes.

Results
The frequency of SSI events, except for those associated with surgery of the upper gastrointestinal tract, revealed a decreasing time-dependent trend. The use of laparoscopic surgery increased dramatically over time (p < 0.01 for the six applicable surgical sites), while the frequency of SSI events during laparoscopic surgery remained unchanged.

Conclusions
The increasing use of laparoscopic surgery was identified, and the observation coincided with the decreasing trend in SSI, especially in lower gastrointestinal tract surgery. If the relationship is causal, the overall SSI incidence among previously healthy individuals is expected to decrease, because the use of laparoscopic surgery has large growth potential in Japan.