bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic analysis of specific and nonspecific auxin effects on endocytosis and trafficking
Authors: Narasimhan Madhumitha , Gallei Michelle , Tan Shutang , Johnson Alexander , Verstraeten Inge , Li Lanxin , Rodriguez Lesia , Han Huibin , Himschoot Ellie , Wang Ren , Vanneste Steffen , Sánchez-Simarro Judit , Aniento Fernando , Adamowski Maciek , Friml Jiří 
Published: March 2021

Abstract
The phytohormone auxin and its directional transport through tissues are intensively studied. However, a mechanistic understanding of auxin-mediated feedback on endocytosis and polar distribution of PIN auxin transporters remains limited due to contradictory observations and interpretations. Here, we used state-of-the-art methods to reexamine the auxin effects on PIN endocytic trafficking. We used high auxin concentrations or longer treatments versus lower concentrations and shorter treatments of natural indole-3-acetic acid (IAA) and synthetic naphthalene acetic acid (NAA) auxins to distinguish between specific and nonspecific effects. Longer treatments of both auxins interfere with Brefeldin A-mediated intracellular PIN2 accumulation and also with general aggregation of endomembrane compartments. NAA treatment decreased the internalization of the endocytic tracer dye, FM4-64; however, NAA treatment also affected the number, distribution, and compartment identity of the early endosome/trans-Golgi network, rendering the FM4-64 endocytic assays at high NAA concentrations unreliable. To circumvent these nonspecific effects of NAA and IAA affecting the endomembrane system, we opted for alternative approaches visualizing the endocytic events directly at the plasma membrane (PM). Using total internal reflection fluorescence microscopy, we saw no significant effects of IAA or NAA treatments on the incidence and dynamics of clathrin foci, implying that these treatments do not affect the overall endocytosis rate. However, both NAA and IAA at low concentrations rapidly and specifically promoted endocytosis of photo-converted PIN2 from the PM. These analyses identify a specific effect of NAA and IAA on PIN2 endocytosis, thus, contributing to its polarity maintenance and furthermore illustrate that high auxin levels have nonspecific effects on trafficking and endomembrane compartments.
Are There Gender Differences in Neck Pain and Musculoskeletal Disorders of the Cervical Spine Associated with Migraine?
Authors: Xavier Nathan da Silva , Benatto Mariana Tedeschi , Florencio Lidiane Lima , Fernández-de-las-Peñas César , Dach Fabiola , Bevilaqua-Grossi Débora 
Published: March 2021

Abstract

Objective
To evaluate gender differences in clinical characteristics of migraine by examining presence and severity of cutaneous allodynia, migraine-related disability, neck pain and its associated disability, passive mobility of the upper cervical spine, and performance of the deep neck flexor muscles.

Design
Cross-sectional study.

Subjects
30 men and 30 women with migraine.

Methods
Participants responded to the questionnaires Migraine Disability Assessment questionnaire, 12-item Allodynia Symptom Checklist, and Neck Disability Index. The mobility of the upper cervical spine was assessed by using the Flexion-Rotation Test. Performance of the deep neck flexor muscles was evaluated by applying the Craniocervical Flexion Test. Comparison of the groups was carried out by using the Student’s t-test or the χ2 test. The prevalence ratio was also calculated.

Results
Women showed a higher prevalence of cutaneous allodynia (P = .001) and a 4 times greater risk of having severe cutaneous allodynia than to men (P = 0.007). No gender differences were observed in migraine-related disability (P = .08). Women showed higher prevalence of self-reported neck pain (P = .03) and increased risk of having this symptom in comparison to men (Prevalence Ratio = 1.69; P = 0.025). However, there were no gender differences in neck pain-related disability (P = .25), mobility of the upper cervical spine (P = .92), or performance of the deep neck flexor muscles (P = .52).

Conclusion
Women with migraine had a higher frequency of self-reported neck pain and higher prevalence and severity of cutaneous allodynia when compared to men. However, the two groups did not differ regarding neck pain-related disability and performance in the physical tests.
Ultrasound, magnetic resonance imaging and radiography of the finger joints in psoriatic arthritis patients
Authors: Polachek Ari , Furer Victoria , Zureik Mirna , Nevo Sharon , Mendel Liran , Levartovsky David , Wollman Jonathan , Aloush Valerie , Tzemah Reut , Elalouf Ofir , Anouk Marina , Berman Mark , Kaufman Ilana , Lahat Yael , Sarbagil-Maman Hagit , Borok Sara , Broyde Adi , Eder Lihi , Paran Daphna , Iluz Moshe , Eshed Iris , Elkayam Ori 
Published: March 2021

Abstract

Objectives
To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA.

Methods
All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK).

Results
The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P &lt; 0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85–96%, PABAK = 0.70–0.92), flexor tenosynovitis (93–98%, PABAK = 0.87–0.96) and extensor paratenonitis (95–98%, PABAK = 0.90–0.97). Agreement between US, MRI and radiography was 96–98% (PABAK = 0.92–0.97) for erosions and 71–93% (PABAK = 0.47–0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5–0.86) and extensor paratenonitis (0.63–0.85) than for flexor tenosynovitis (0.1–0.75), while the specificity was high for each pathology (0.89–0.98).

Conclusion
There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.
The role of reputation systems in digital discrimination
Authors: Kas Judith , Corten Rense , van de Rijt Arnout 
Published: March 2021

AbstractReputation systems are commonplace in online markets, such as on peer-to-peer sharing platforms. These systems have been argued to be a solution to (ethnic) discrimination on such platforms. This argument is based on empirical studies showing that ethnic disadvantages are smaller for users with ratings than for users without ratings. We argue that this conclusion may be premature, because minorities have a harder time accumulating ratings. The greater benefit of ratings to minorities may be offset by their troubles acquiring any, thereby diminishing the potential for reputation systems to reduce discrimination. We tested this counterargument using a unique data set that contains information on all interactions on a peer-to-peer motorcycle rental platform. We find that the reputation system does not reduce initial inequalities between otherwise comparable renters of different ethnicity. Platforms that wish to reduce discrimination should not only make their reputation system more effective, but also help users collect ratings.
An exploratory focus group study on experiences with snakebites: health-seeking behaviour and challenges in rural communities of Kenya
Authors: van Oirschot Janneke , Ooms Gaby I , Okemo Dorothy J , Waldmann Benjamin , Reed Tim 
Published: March 2021

Abstract

Background
Snakebite envenoming is a long-hidden public health threat in the rural communities of Kenya. This study aimed to shed light on the health-seeking behaviour of people bitten by snakes, views on prevention measures and community needs and the consequences for snakebite patients in these areas.

Methods
Six focus group interviews were conducted in communities in the Kajiado (n=3) and Kilifi (n=3) counties.

Results
Traditional first-aid practices such as the use of a tourniquet and/or cutting the wound, use of a black stone and a variety of other traditional remedies were common. Challenges with transportation to health facilities and inadequately resourced facilities complicated accessing medical care. Community members voiced a need to improve access to trained healthcare workers and snakebite treatments at health facilities.

Conclusion
While communities had high trust in evidence-based medical care, traditional treatment was often sought, causing delays in timely medical attention. Traditional practices were often used in the home environment and these were not usually administered by a traditional healer. The findings illustrate the need to combine improving the availability of effective snakebite treatment and healthcare worker training on snakebite with community education to reduce the impact of snakebite.
What We Learn about Girls’ Education from Interventions That Do Not Focus on Girls
Authors: Evans David K , Yuan Fei 
Published: March 2021

AbstractWhat is the best way to improve access and learning outcomes for girls? This review brings together evidence from 267 educational interventions in 54 low- and middle-income countries – regardless of whether the interventions specifically target girls – and identifies their impacts on girls. To improve access and learning, general interventions deliver average gains for girls that are comparable to girl-targeted interventions. General interventions have similar impacts for girls as for boys. Taken together, these findings suggest that many educational gains for girls may be achieved through nontargeted programs. Many of the most effective interventions to improve access for girls relax household-level constraints (such as cash transfer programs), and many of the most effective interventions to improve learning for girls involve improving the pedagogy of teachers. Girl-targeted interventions may make the most sense when addressing constraints that are unique to, or most pronounced for, girls.
Reduction of leukemic burden via bone‐targeted nanoparticle delivery of an inhibitor of C‐chemokine (C‐C motif) ligand 3 (CCL3) signaling
Authors: Ackun‐Farmmer Marian A. , Soto Celia A. , Lesch Maggie L. , Byun Daniel , Yang Lila , Calvi Laura M. , Benoit Danielle S. W. , Frisch Benjamin J. 
Published: March 2021

AbstractLeukemias are challenging diseases to treat due, in part, to interactions between leukemia cells and the bone marrow microenvironment (BMME) that contribute significantly to disease progression. Studies have shown that leukemic cells secrete C‐chemokine (C‐C motif) ligand 3 (CCL3), to disrupt the BMME resulting in loss of hematopoiesis and support of leukemic cell survival and proliferation. In this study, a murine model of blast crisis chronic myelogenous leukemia (bcCML) that expresses the translocation products BCR/ABL and Nup98/HoxA9 was used to determine the role of CCL3 in BMME regulation. Leukemic cells derived from CCL3−/− mice were shown to minimally engraft in a normal BMME, thereby demonstrating that CCL3 signaling was necessary to recapitulate bcCML disease. Further analysis showed disruption in hematopoiesis within the BMME in the bcCML model. To rescue the altered BMME, therapeutic inhibition of CCL3 signaling was investigated using bone‐targeted nanoparticles (NP) to deliver Maraviroc, an inhibitor of C‐C chemokine receptor type 5 (CCR5), a CCL3 receptor. NP‐mediated Maraviroc delivery partially restored the BMME, significantly reduced leukemic burden, and improved survival. Overall, our results demonstrate that inhibiting CCL3 via CCR5 antagonism is a potential therapeutic approach to restore normal hematopoiesis as well as reduce leukemic burden within the BMME.
Follicle‐stimulating hormone promotes growth of human prostate cancer cell line‐derived tumor xenografts
Authors: Oduwole Olayiwola O. , Poliandri Ariel , Okolo Anthony , Rawson Phil , Doroszko Milena , Chrusciel Marcin , Rahman Nafis A. , Serrano de Almeida Gilberto , Bevan Charlotte L. , Koechling Wolfgang , Huhtaniemi Ilpo T. 
Published: March 2021

AbstractChemical castration in prostate cancer can be achieved with gonadotropin‐releasing hormone (GnRH) agonists or antagonists. Their effects differ by the initial flare of gonadotropin and testosterone secretion with agonists and the immediate pituitary‐testicular suppression by antagonists. While both suppress luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) initially, a rebound in FSH levels occurs during agonist treatment. This rebound is potentially harmful, taken the expression of FSH receptors (R) in prostate cancer tissue. We herein assessed the role of FSH in promoting the growth of androgen‐independent (PC‐3, DU145) and androgen‐dependent (VCaP) human prostate cancer cell line xenografts in nude mice. Gonadotropins were suppressed with the GnRH antagonist degarelix, and effects of add‐back human recombinant FSH were assessed on tumor growth. All tumors expressed GnRHR and FSHR, and degarelix treatment suppressed their growth. FSH supplementation reversed the degarelix‐evoked suppression of PC‐3 tumors, both in preventive (degarelix and FSH treatment started upon cell inoculation) and therapeutic (treatments initiated 3 weeks after cell inoculation) setting. A less marked, though significant FSH effect occurred in DU145, but not in VCaP xenografts. FSHR expression in the xenografts supports direct FSH stimulation of tumor growth. Testosterone supplementation, to maintain the VCaP xenografts, apparently masked the FSH effect on their growth. Treatment with the LH analogue hCG did not affect PC‐3 tumor growth despite their expression of luteinizing hormone/choriongonadotropin receptor. In conclusion, FSH, but not LH, may directly stimulate the growth of androgen‐independent prostate cancer, suggesting that persistent FSH suppression upon GnRH antagonist treatment offers a therapeutic advantage over agonist.
Proteomic and phospholipidomic characterization of extracellular vesicles inducing tumor microenvironment in Epstein‐Barr virus‐associated lymphomas
Authors: Ito Masatoshi , Kudo Kai , Higuchi Hiroshi , Otsuka Hiroko , Tanaka Masayuki , Fukunishi Nahoko , Araki Takuma , Takamatsu Masako , Ino Yoko , Kimura Yayoi , Kotani Ai 
Published: March 2021

AbstractEpstein‐Barr virus (EBV) causes malignant carcinomas including B cell lymphomas accompanied by the systemic inflammation. Previously, we observed that phosphatidylserine (PS)‐exposing subset of extracellular vesicles (EVs) secreted from an EBV strain Akata‐transformed lymphoma (Akata EVs) convert surrounding phagocytes into tumor‐associated macrophages (TAMs) via induction of inflammatory response, which is in part mediated by EBV‐derived micro RNAs. However, it is still unclear about EV‐carried other potential inflammatory factors associated with TAM formation in EBV lymphomas. To this end, we sought to explore proteomic and phospholipidomic profiles of PS‐exposing EVs derived from EBV‐transformed lymphomas. Mass spectrometric analysis revealed that several immunomodulatory proteins including integrin αLβ2 and fibroblast growth factor 2 (FGF2) were highly expressed in PS‐exposing Akata EVs compared with another EBV strain B95‐8‐transformed lymphoma‐derived counterparts which significantly lack TAM‐inducing ability. Pharmacological inhibition of either integrin αLβ2 or FGF2 hampered cytokine induction in monocytic cultured cells elicited by PS‐exposing Akata EVs, suggesting the involvement of these proteins in EV‐mediated TAM induction in EBV lymphomas. In addition, phospholipids containing precursors of immunomodulatory lipid mediators were also enriched in PS‐exposing Akata EVs compared with B95‐8 counterparts. Phospholipidomic analysis of fractionated Akata EVs by density gradient centrifugation further demonstrated that PS‐exposing Akata EVs might be identical to certain Akata EVs in low density fractions containing exosomes. Therefore, we concluded that a variety of immunomodulatory cargo molecules in a certain EV subtype are presumably conducive to the development of EBV lymphomas.
Prevalence and Clinical Characteristics of Patients With Sepsis Discharge Diagnosis Codes and Short Lengths of Stay in U.S. Hospitals
Authors: Kuye Ifedayo , Anand Vijay , Klompas Michael , Chan Christina , Kadri Sameer S. , Rhee Chanu 
Published: March 2021

Objectives:
Some patients diagnosed with sepsis have very brief hospitalizations. Understanding the prevalence and clinical characteristics of these patients may provide insight into how sepsis diagnoses are being applied as well as the breadth of illnesses encompassed by current sepsis definitions.

Design:
Retrospective observational study.

Setting:
One-hundred ten U.S. hospitals in the Cerner HealthFacts dataset (primary cohort) and four hospitals in Eastern Massachusetts (secondary cohort used for detailed medical record reviews).

Patients:
Adults hospitalized from April 2016 to December 2017.

Interventions:
None.

Measurements and Main Results:
We identified hospitalizations with International Classification of Diseases, 10th Edition codes for sepsis (including sepsis, septicemia, severe sepsis, and septic shock) and compared “short stay sepsis” patients (defined as discharge alive within 3 d) versus nonshort stay sepsis patients using detailed electronic health record data. In the Cerner cohort, 67,733 patients had sepsis discharge diagnosis codes, including 6,918 (10.2%) with short stays. Compared with nonshort stay sepsis patients, short stay patients were younger (median age 60 vs 67 yr) and had fewer comorbidities (median Elixhauser score 5 vs 13), lower rates of positive blood cultures (8.2% vs 24.1%), lower rates of ICU admission (6.2% vs 31.6%), and less frequently had severe sepsis/septic shock codes (13.5% vs 36.6%). Almost all short stay and nonshort stay sepsis patients met systemic inflammatory response syndrome criteria at admission (84.5% and 87.5%, respectively); 47.2% of those with short stays had Sequential Organ Failure Assessment scores of 2 or greater at admission versus 73.2% of those with longer stays. Findings were similar in the secondary four-hospital cohort. Medical record reviews demonstrated that physicians commonly diagnosed sepsis based on the presence of systemic inflammatory response syndrome criteria, elevated lactates, or positive blood cultures without concurrent organ dysfunction.

Conclusions:
In this large U.S. cohort, one in 10 patients coded for sepsis were discharged alive within 3 days. Although most short stay patients met systemic inflammatory response syndrome criteria, they met Sepsis-3 criteria less than half the time. Our findings underscore the incomplete uptake of Sepsis-3 definitions, the breadth of illness severities encompassed by both traditional and new sepsis definitions, and the possibility that some patients with sepsis recover very rapidly.
Identifying sensitive windows of airborne lead exposure associated with behavioral outcomes at age 12
Authors: Rasnick Erika , Ryan Patrick H. , Bailer A. John , Fisher Thomas , Parsons Patrick J. , Yolton Kimberly , Newman Nicholas C. , Lanphear Bruce P. , Brokamp Cole 
Published: March 2021

Background:
Despite the precipitous decline of airborne lead concentrations following the removal of lead in gasoline, lead is still detectable in ambient air in most urban areas. Few studies, however, have examined the health effects of contemporary airborne lead concentrations in children.

Methods:
We estimated monthly air lead exposure among 263 children (Cincinnati Childhood Allergy and Air Pollution Study; Cincinnati, OH; 2001–2005) using temporally scaled predictions from a validated land use model and assessed neurobehavioral outcomes at age 12 years using the parent-completed Behavioral Assessment System for Children, 2nd edition. We used distributed lag models to estimate the effect of airborne lead exposure on behavioral outcomes while adjusting for potential confounding by maternal education, community-level deprivation, blood lead concentrations, greenspace, and traffic related air pollution.

Results:
We identified sensitive windows during mid- and late childhood for increased anxiety and atypicality scores, whereas sensitive windows for increased aggression and attention problems were identified immediately following birth. The strongest effect was at age 12, where a 1 ng/m3 increase in airborne lead exposure was associated with a 3.1-point (95% confidence interval: 0.4, 5.7) increase in anxiety scores. No sensitive windows were identified for depression, somatization, conduct problems, hyperactivity, or withdrawal behaviors.

Conclusions:
We observed associations between exposure to airborne lead concentrations and poor behavioral outcomes at concentrations 10 times lower than the National Ambient Air Quality Standards set by the US Environmental Protection Agency.
Reconstruction of the Midfoot Area with Vascularized Chimeric Osteocutaneous Scapula Flap: A Case Report
Authors: Arata Jun , Tsuge Itaru , Kumakiri Masanori , Yamashita Teruyo , Kaito Shuko , Yong Yoon , Yamada Shigeru 
Published: March 2021

Summary:
We report a case of reconstruction of a left midfoot defect with a chimeric partial scapula and skin flap in a 20-year-old man. After radical debridement, bone and soft tissue defects were reconstructed with a chimeric scapula and skin flap. The postoperative course was uneventful. The patient could walk well without support, and bone union was achieved 6 months after surgery. In 14 months of follow-up, no clinical complications (including new ulcer or stress fracture) were noted and full ambulation was achieved, with the patient returning to his previous work. We suggest that the chimeric scapula and skin flap may be a useful alternative option for midfoot reconstruction.
The prognostic value of IL-8 for the death of severe or critical patients with COVID-19
Authors: Li Hui , Zhang Jun , Fang Chen , Zhao Xuming , Qian Bin , Sun Yihui , Zhou Yan , Hu Ji , Huang Yun , Ma Qi , Hui Jie 
Published: March 2021

Abstract
Inflammation has been believed to contribute to coronavirus disease 2019 (COVID-19). Risk factors for death of COVID-19 pneumonia have not yet been well established.
In this retrospective cohort study, we included the deceased patients in COVID-19 specialized ICU with laboratory-confirmed COVID-19 from Guanggu hospital area of Tongji Hospital from February 8th to March 30th. Demographic, clinical, laboratory, and outcome data were extracted from electronic medical records using a standard data collection form. We used Spearman rank correlation and Cox regression analysis to explore the risk factors associated with in-hospital death, especially the association between inflammatory cytokines and death.
A total of 205 severe/critical COVID-19 pneumonia patients were admitted in the COVID-19 specialized ICU and 75 deceased patients were included in the final analysis. The median age of the deceasing patients was 70 years (IQR 65–79). The common symptoms were fever (78.9%), cough (70.4%), and expectoration (39.4%). The BNP and CRP levels were far beyond the normal reference range. In the Spearman rank correlation analysis, IL-8 was found to be significantly associated with the time from onset to death (rs= −0.30, P = .034) and that from admission to death (rs= −0.32, P = .019). Cox regression showed after adjusting age and sex, IL-8 levels were still significantly associated with the time from onset to death (P = .003) and that from admission to death (P
= .01).
IL-8 levels were associated with in-hospital death in severe/critical COVID-19 patients, which could help clinicians to identify patients with high risk of death at an early stage.