bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double‐masked, vehicle‐controlled study
Authors: Stefansson Einar , Loftsson Thorstein , Larsen Michael , Papp András , Kaarniranta Kai , Munk Marion R. , Dugel Pravin , Tadayoni Ramin ,   DX‐211 study group
Published: July 2022

AbstractPurposeTo evaluate topical dexamethasone ophthalmic suspension OCS‐01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME).MethodsThis was a multicenter, double‐masked, parallel‐group, randomized, Phase 2 study. Patients aged 18–85 years with DME of <3 years duration, ETDRS central subfield thickness ≥ 310 μm by SD‐OCT, and ETDRS letter score ≤ 73 and ≥ 24 in the study eye were randomized 2:1 to OCS‐01 or matching vehicle, 1 drop 3 times/day for 12 weeks. Efficacy was evaluated as change from baseline to Week 12 of ETDRS letter score and central macular thickness (CMT). The primary analysis used a linear model with baseline ETDRS letters as a covariate, and missing data imputed using multiple imputation pattern mixture model techniques. Active treatment was considered superior to vehicle if the one‐sided p‐value was <0.15 and the difference in mean change from baseline in ETDRS letters was >0.ResultsMean CMT showed a greater decrease from baseline with OCS‐01 (N = 99) than vehicle (N = 45) at Week 12 (−53.6 vs −16.8 μm, p = 0.0115), with significant differences favouring OCS‐01 from Weeks 2 to 12. OCS‐01 was well‐tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS‐01 and 1 letter with vehicle (p = 0.125). In a post‐hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS‐01 group improved 3.8 letters compared with 0.9 letters with vehicle.ConclusionTopical OCS‐01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision.
Impact of germline HLA genotypes on clinical outcomes in patients with urothelial cancer treated with pembrolizumab
Authors: Takahashi Shuhei , Narita Shintaro , Fujiyama Nobuhiro , Hatakeyama Shingo , Kobayashi Takashi , Kato Renpei , Naito Sei , Sakatani Toru , Kashima Soki , Koizumi Atsushi , Yamamoto Ryohei , Nara Taketoshi , Kanda Souhei , Numakura Kazuyuki , Saito Mitsuru , Obara Wataru , Tsuchiya Norihiko , Ohyama Chikara , Ogawa Osamu , Habuchi Tomonori 
Published: July 2022

AbstractHuman leukocyte antigen class I (HLA‐I) genotypes are suggested to influence the cancer response to checkpoint blockade immunotherapy. This study assessed the impact of germline HLA genotypes on clinical outcomes in patients with chemoresistant advanced urothelial cancer (UC) treated with pembrolizumab. Zygosity, supertypes, evolutionary divergency, and specific alleles of germline HLA‐I and ‐II were evaluated using the Luminex technique in 108 patients with chemoresistant metastatic or locally advanced UC treated with pembrolizumab. Among the 108 patients, 69 died and 83 showed radiographic progression during follow‐up. Homozygous for at least one HLA‐I locus, absence of the HLA‐A03 supertype, and high HLA‐I evolutionary divergence were associated with a radiographic response, but were not associated with survival outcomes. Patients with the HLA‐DQB1*03:01 allele had significantly lower disease control rates than patients without the allele (17.4% vs. 53.8%, p = 0.002); its presence was also an independent risk factor for progressive disease (hazard ratio 4.35, 95% confidence interval 1.03–18.46). Furthermore, patients with the HLA‐DQB1*03:01 allele had significantly worse progression‐free survival than patients without the allele (median progression‐free survival 3.1 vs. 4.8 months, p = 0.035). There was no significant relationship between any HLA status and the incidence of severe adverse events. Several germline HLA genotypes, especially HLA‐DQB1*03:01, may be associated with radiographic progression. However, their impact on treatment response is limited, and germline HLA genotypes was not independently associated with survival outcomes. Further prospective studies are needed to confirm the relationship between germline HLA genotypes and clinical outcomes in patients with chemoresistant advanced UC treated with pembrolizumab.
Combination therapy with anamorelin and a myostatin inhibitor is advantageous for cancer cachexia in a mouse model
Authors: Hanada Kako , Fukasawa Kunpei , Hinata Hiroki , Imai Shú , Takayama Kentaro , Hirai Hideyo , Ohfusa Rina , Hayashi Yoshio , Itoh Fumiko 
Published: July 2022

AbstractCancer cachexia is a multifactorial disease that causes continuous skeletal muscle wasting. Thereby, it seems to be a key determinant of cancer‐related death. Although anamorelin, a ghrelin receptor agonist, has been approved in Japan for the treatment of cachexia, few medical treatments for cancer cachexia are currently available. Myostatin (MSTN)/growth differentiation factor 8, which belongs to the transforming growth factor‐β family, is a negative regulator of skeletal muscle mass, and inhibition of MSTN signaling is expected to be a therapeutic target for muscle‐wasting diseases. Indeed, we have reported that peptide‐2, an MSTN‐inhibiting peptide from the MSTN prodomain, alleviates muscle wasting due to cancer cachexia. Herein, we evaluated the therapeutic benefit of myostatin inhibitory D‐peptide‐35 (MID‐35), whose stability and activity were more improved than those of peptide‐2 in cancer cachexia model mice. The biologic effects of MID‐35 were better than those of peptide‐2. Intramuscular administration of MID‐35 effectively alleviated skeletal muscle atrophy in cachexia model mice, and the combination therapy of MID‐35 with anamorelin increased food intake and maximized grip strength, resulting in longer survival. Our results suggest that this combination might be a novel therapeutic tool to suppress muscle wasting in cancer cachexia.
Effect of fasting on cancer: A narrative review of scientific evidence
Authors: Tiwari Sagun , Sapkota Namrata , Han Zhenxiang 
Published: July 2022

AbstractEmerging evidence suggests that fasting could play a key role in cancer treatment by fostering conditions that limit cancer cells' adaptability, survival, and growth. Fasting could increase the effectiveness of cancer treatments and limit adverse events. Yet, we lack an integrated mechanistic model for how these two complicated systems interact, limiting our ability to understand, prevent, and treat cancer using fasting. Here, we review recent findings at the interface of oncology and fasting metabolism, with an emphasis on human clinical studies of intermittent fasting. We recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy and reduce side effects in cancer patients.
Working and caring for a disabled adopted child during a pandemic
Authors: Sellmaier Claudia , Kim JaeRan 
Published: July 2022

AbstractIntegrating work and family demands can be challenging for families caring for a child with one or more disabilities. The pandemic and its changes to work, schooling and service delivery potentially added to these challenges. This exploratory mixed methods study sought to understand how the pandemic affected adoptive parents' work–life fit and service use. A total of 200 participants responded to survey questions about parenting an adopted child with a disability prior to, and after, the onset of Covid‐19. More than half of the parents (59.2%) reported that it was somewhat to very difficult to integrate both work and family demands. Parents with greater access to workplace flexibility and supportive supervisors had significantly less difficulties combining work and family. Families who reported more problems with accessing mental health services, special education and respite care reported significantly more challenges with work–family fit. Parents reported increased stress due to the pandemic changes, but many also shared positive changes such as more time for family. Online services were experienced as effective for some children and reduced time spent driving to appointments. Recommendations for workplace and social service practice and policy supporting adoptive parents of children with disabilities are discussed.
Heart transplantation in Val142Ile mutation in the modern era: A single center experience
Authors: Lyle Melissa A. , Brown Matthew T. , Morris Alanna A. , Gupta Divya , Vega J. David , Cole Robert T. , Bhatt Kunal N. 
Published: July 2022

AbstractLittle is known about the post heart transplantation management of extra cardiac manifestations in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR‐CM) in the new era of disease modifying treatment for ATTR amyloidosis. This is a retrospective study of all patients with hATTR‐CM associated with the Val142Ile variant who underwent heart transplantation (HT) from January 2014 to February 2022. All 10 patients with the Val142Ile mutation were successfully transplanted, with a 1 year survival post heart transplantation (HT) of 90%, comparable to an age, sex, and race matched cohort of patients transplanted for non‐amyloid indications. However, 4 (40%) of these patients developed progressive extracardiac manifestations requiring initiation of TTR silencer therapy with the small interfering RNA (siRNA) drug patisiran, which was well tolerated with no significant side effects in this population. We recommend formal neurologic evaluation and assessment of extracardiac manifestations annually as part of routine post‐transplant care, and disease modifying therapy, aimed at TTR stabilization or silencing, should be initiated in the context of previously untreated extracardiac manifestations or evidence of subclinical neuropathy to prevent progression.
Induction therapy in lung transplantation: A contemporary analysis of trends and outcomes
Authors: Shagabayeva Larisa , Osho Asishana A. , Moonsamy Philicia , Mohan Navyatha , Li Selena Shi‐Yao , Wolfe Stanley , Langer Nathaniel B. , Funamoto Masaki , Villavicencio Mauricio A. 
Published: July 2022

AbstractObjectivesWe provide a contemporary consideration of long‐term outcomes and trends of induction therapy use following lung transplantation in the United States. Methods: We reviewed the United Network for Organ Sharing registry from 2006 to 2018 for first‐time, adult, lung‐only transplant recipients. Long‐term survival was compared between induction classes (Interleukin‐2 inhibitors, monoclonal or polyclonal cell‐depleting agents, and no induction therapy). A 1:1 propensity score match was performed, pairing patients who received basiliximab with similar risk recipients who did not receive induction therapy. Outcomes in matched populations were compared using Cox, Kaplan‐Meier and Logistic regression modeling.Measurements and main results22 025 recipients were identified; 8003 (36.34%) were treated with no induction therapy, 11 045 (50.15%) with basiliximab, 1556 (7.06%) with alemtuzumab and 1421 (6.45%) with anti‐thymocyte globulin. Compared with those who received no induction, patients receiving basiliximab, alemtuzumab or anti‐thymocyte globulin were found on multivariable Cox‐regression analyses to have lower long‐term mortality (all p < .05). Following propensity score matching of basiliximab and no induction populations, analyses demonstrated a statistically significant association between basiliximab use and long‐ term survival (p < .001). Basiliximab was also associated with a lower risk of acute rejection (p < .001) and renal failure (p = .002).ConclusionInduction therapy for lung transplant recipients—specifically basiliximab—is associated with improved long‐term survival and a lower risk of renal failure or acute rejection.
Urgent use of voxelotor in sickle cell disease when immediate transfusion is not safe
Authors: Ferlis Mica , Lipato Thokozeni , Roseff Susan D. , Smith Wally R. 
Published: July 2022

AbstractThe use of blood transfusions to improve anemia resulting from sickle cell disease (SCD) is often limited by alloimmunization, which occurs due to exposure to incompatible antigen present on donor red blood cells (RBCs). This complication occasionally manifests as delayed hemolytic transfusion reactions (DHTRs) that cause hemolysis of the recipient's own RBCs and can lead to fatal anemia. In this case study, we report a patient with SCD who experienced a DHTR following chronic transfusion and was successfully treated with voxelotor, an orally administered sickle hemoglobin (HbS) polymerization inhibitor for the treatment of SCD. Laboratory tests following admission indicated pan‐reactivity in antigens, and a rare donor registry was used to locate acceptable units. The patient experienced the DHTR 3 days after admission, which limited laboratory tests due to profound hemolysis. Alternative treatments were limited, and phenotypically matched units were incompatible, so voxelotor was selected as a last‐resort treatment. Following initiation of voxelotor 1500 mg, the patient's hemoglobin levels returned to baseline (6 g/dl) within 10 days, with clinical improvements. This report provides evidence regarding the use of voxelotor in the treatment of profound anemia where other treatments could be unsafe or unavailable.
Non‐exchangeable stable hydrogen isotope ratios in clay minerals and soil clay fractions: A method test
Authors: Merseburger Stefan , Kessler Arnim , Oelmann Yvonne , Wilcke Wolfgang 
Published: July 2022

AbstractStable hydrogen isotope ratios (δ2H values) in structural hydroxyl groups of pedogenic clay minerals are inherited from the surrounding water at the time of their formation. Only non‐exchangeable H preserves the environmental forensic and paleoclimate information (δ2Hn value). To measure δ2Hn values in structural H of clay minerals and soil clay fractions, we adapted a steam equilibration method by accounting for high hygroscopicity. Our δ2Hn values for USGS57 biotite (−95.3 ± SD 0.9‰) and USGS58 muscovite (30.7 ± 1.4‰) differed slightly but significantly from the reported δ2H values (−91.5 ± 2.4‰ and −28.4 ± 1.6‰), because the minerals contained 1.1%–4.4% of exchangeable H. The low SD of replicate measurements (n = 3) confirmed a high precision. The clay separation method including destruction of Fe oxides, carbonates and soil organic matter, and dispersion did not significantly change the δ2Hn values of five different clay minerals. However, we were unable to remove all organic matter from the soil clay fractions resulting in an estimated bias of 1‰ in two samples and 15‰ in the carbon‐richest sample. Our results demonstrate that δ2Hn values of structural H of clay minerals and soil clay fractions can be reliably measured without interference from atmospheric water and the method used to separate the soil clay fraction.Highlights
We tested steam equilibration to determine stable isotope ratios of structural H in clay.
Gas‐tight capsule sealing in Ar atmosphere was necessary to avoid remoistening.
Our steam equilibration method showed a high accuracy and precision.
The clay separation method did not change stable isotope ratios of structural H in clay.
Predictive validity of the modified Kihon Checklist for the incidence of functional disability among older people: A 3‐year cohort study from the JAGES
Authors: Watanabe Ryota , Tsuji Taishi , Ide Kazushige , Noguchi Taiji , Yasuoka Mikako , Kamiji Koto , Satake Shosuke , Kondo Katsunori , Kojima Masayo 
Published: July 2022

AimThe original Kihon Checklist, validated to predict the incidence of functional disability, has been modified to capture both functional ability (can/cannot) and performing state (do/do not). However, the predictive validity of the modified Kihon Checklist remains unverified. Therefore, this study intends to verify the predictive validity of the modified Kihon Checklist and to clarify whether predictive discrimination differs between the classification method of functional ability and performing state.MethodsThe participants comprised 67 398 older people who responded to the Japan Gerontological Evaluation Study (2016). They were followed for 3.1 years on average. Cox's proportional hazards model with incidence of functional disability as the endpoint was used to calculate the hazard ratio, adjusted for sex and age. The independent variables were judged by two classification methods, functional ability and performing state, using nine indicators based on the modified Kihon Checklist. Additionally, we examined whether the two classification methods produced different C‐index estimates.ResultsIncidence of functional disability occurred in 6232 participants (9.2%). The adjusted hazard ratio of those to whom the nine indicators applied was significantly higher than that of those to whom they did not. The range of the hazard ratio was 1.50–3.82 for both classification methods. The C‐index was slightly higher when the classification was based on performing state than when it was based on on functional ability.ConclusionsAlthough predictive discrimination was slightly higher for the performing state than for functional ability, the predictive validity of the modified Kihon Checklist was confirmed for both. Geriatr Gerontol Int 2022; 22: 667–674.
Phytotherapy in urological benign disease: A systematic review
Authors: Villa Giulia , Boarin Mattia , Rosa Debora , Togni Serena , Manara Duilio F. , Bonetti Loris , Terzoni Stefano 
Published: July 2022

AbstractWhat is the state of knowledge on the use of phytotherapy in the following urological benign diseases: prostatic hyperplasia, erectile dysfunction, male infertility, urolithiasis and low‐urinary tract symptoms? Supplements derived from natural products are used in medicine alone or in combination with drugs. In urology, there are many products used for symptom management in benign conditions. The aim of this review was to investigate the use of herbal medicines to treat benign urological diseases. A systematic review was conducted using the PubMed, CINAHL, Cochrane Library, Embase and Scopus (2010–2021) databases. The inclusion criteria were studies describing the use of phytotherapeutic strategies to treat adult patients with urological diseases. Quality assessments were performed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Nineteen studies were included in this systematic review: 13 randomized controlled trials, 3 pilot studies, 1 quasi‐experimental study, 1 retrospective observational study and 1 post hoc analysis. Phytotherapeutic agents used to treat benign prostatic hyperplasia included royal jelly, Viola odorata, Echium amoenum, Physalis alkekengi, soy isoflavones, Serenoa repens, Trigonella foenum‐graecum, lycopene and selenium. Tribulus terrestris is widely used to treat erectile dysfunction and male infertility. Lycopene, Korean ginseng berries, Indian ginseng and Curcuma improve sperm characteristics and motility. Lupeol therapy reduces kidney stone size, improving urolithiasis symptoms and accelerating the expulsion of small stones. No standard of care has been established for the use of phytotherapeutic agents to manage patients with symptomatic urological disorders. Although randomized controlled trials were the most common study type in our review, the sample sizes were limited, and the study duration and follow‐up periods were often very short.
Prostatitis‐like symptoms in Antioquia, Colombia using the National Institute of Health‐Chronic Prostatitis Symptom Index
Authors: Puerta Suárez Jenniffer , Cardona Maya Walter Darío 
Published: July 2022

AbstractThe aim of the present study is to find the frequency of chronic prostatitis in Antioquia, Colombia. There are epidemiological gaps in this issue in the Colombian population. Chronic prostatitis is a prevalent disease with a high impact on life quality. The NIH‐Chronic Prostatitis Symptom Index (NIH‐CPSI) is a commonly used 13‐item questionnaire to assess symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. A validated Spanish version of the NIH‐CPSI questionnaire was distributed through social media and institutional e‐mails from the University of Antioquia database and other institutions in the Metropolitan Area. Of the distributed questionnaires, 2022 were filled. The vast majority of participants were students, teachers, and professionals. A frequency of 16.4% chronic prostatitis symptoms was observed, 10.1% of individuals had severe symptoms with a median age of 32 years, accompanied by perineal pain and ejaculatory symptoms. Using the NIH‐CPSI, the reported worldwide prevalence of chronic prostatitis is range between 1.8% and 65%. This report shows the disease's frequency in Colombia and Latin America for the first time. Chronic prostatitis is a frequent disease in the Antioquia population, with a high impact on the quality of life. Therefore, public health policies should be implemented focusing on men's health.
Less timely earnings announcements and voluntary disclosure
Authors: Cho Hyunkwon , Choi Sunhwa , Kim Robert 
Published: July 2022

AbstractThe release of earnings information has become less timely in recent years partly because firms increasingly disclose earnings concurrently with their periodic reports (e.g., 10‐Ks, 10‐Qs). We examine whether firms use voluntary disclosure to mitigate the negative economic consequences of less timely earnings announcements (EAs). We find that firms with less timely EAs are more likely to provide voluntary 8‐K filings over the period leading to the EA. We also find that investors’ demand for timely information, the nature of earnings news and litigation risk affect the extent to which firms provide voluntary disclosure to compensate for less timely EAs. The negative effect of less timely EAs on information asymmetry is attenuated when firms provide voluntary 8‐K filings prior to EAs. Overall, our findings suggest that firms voluntarily communicate with investors using voluntary disclosure when their EAs are less timely.
Pustular diseases and keratinocyte–myeloid synergy
Authors: Christophers E. , Schröder J. M. 
Published: July 2022

AbstractPustules are among the most common lesions produced in human skin. Infections by pathogens and drug‐induced reactions are frequent causes of pustule formation. In recent years immune‐mediated pustular diseases have drawn attention. It is proposed to classify pustular diseases according to the initiating events and sites: purely epidermal pustules, follicular pustules or pustules noted in autoinflammatory syndromes. The unifying pathology in all of the three categories is a microinvasion of activated neutrophils into epidermal or adnexal epithelia. Formation of pustules involves established IL‐17 / IL‐23, IL‐36 / IL‐36RN driven pathology, or IL‐1 /caspase‐activated autoinflammation. Pathophysiology demonstrates an intriguing synergy of keratinocytes with neutrophils. This is called keratinocyte–myeloid synergy (KMS). Non‐infectious pustules are formed by IFNα controlling the production of chemoattractants (IL‐8, LTB4) or induced by IL‐1‐regulated inflammasomes and caspase/ IFNβ‐induced chemotaxins. The presence of physical barriers, for example, cornified cell layers (str. corneum), is instrumental in establishing chemotactic gradients and blocking migrating neutrophils. In follicular KMS‐driven pustular disorders, in contrast to epidermal pustules, neutrophil‐mediated toxicity propagates lasting and expanding ulcerating diseases with increased levels of circulating immunoglobulin A (IgA). Complexed IgA is suggested to propagate ongoing pustular diseases. These are prerequisites essential for developing pustules in burdensome human skin diseases.