bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical therapies in the decongestive treatment of lymphedema: A randomized, non-inferiority controlled study
Authors: Forner-Cordero Isabel , Muñoz-Langa José , DeMiguel-Jimeno Juan María , Rel-Monzó Pilar 
Published: September 2021

Objective: To assess whether the treatment with intermittent pneumatic compression plus multilayer bandages is not inferior to classical trimodal therapy with manual lymphatic drainage in the decongestive lymphedema treatment. Study Design: Randomized, non-inferiority, controlled study to compare the efficacy of three physical therapies’ regimens in the Decongestive Lymphatic Therapy. Participants: 194 lymphedema patients, stage II–III with excess volume > 10% were stratified within upper and lower limb and then randomized to one of the three treatment groups. Baseline characteristics were comparable between the groups. Intervention: all patients were prescribed 20 sessions of the following regimens: Group A (control group): manual lymphatic drainage + Intermittent Pneumatic Compression + Bandages; Group B: pneumatic lymphatic drainage + Intermittent Pneumatic Compression + Bandages; and Group C: only Intermittent Pneumatic Compression + Bandages. End-point: Percentage reduction in excess volume (PREV). Results: All patients improved after treatment. Global mean of PREV was 63.9%, without significant differences between the groups. The lower confidence interval of the mean difference in PREV between group B and group A, and between group C and group A were below 15%, thus meeting the non-inferiority criterion. Most frequent adverse events were discomfort and lymphangitis, without differences between groups. A greater baseline edema, an upper-limb lymphedema and a history of dermatolymphangitis were independent predictive factors of worse response in the multivariate analysis. Conclusions: Decongestive lymphatic therapy performed only with intermittent pneumatic compression plus bandages is not inferior to the traditional trimodal therapy with manual lymphatic drainage. This approach did not increase adverse events.
Risk of Severe Acute Localized Reactions for Different Intraarticular Hyaluronic Acid Knee Injections in a Real-World Setting
Authors: Ong Kevin L. , Farr Jack , Gudeman Andrew S. , Murray Iain R. , McIntyre Louis F. , Hummer Charles D. , Ngai Wilson , Lau Edmund , Altman Roy D. , Sherman Seth L. 
Published: September 2021

Objective: Case reports of severe acute localized reactions (SALR) following intraarticular (IA) hyaluronic acid (HA) injections for knee osteoarthritis (OA) have been described. We compared surrogate SALR measures between patients using hylan G-F 20 and specific non-hylan G-F 20 HA products. Design: Knee OA patients were identified from the Optum Clinformatics dataset (January 2006 to June 2016), stratified into hylan G-F 20 and non-hylan G-F 20 HA users, matched by single or multiple injection products. Occurrences of surrogate SALR measures including inflammation/infection, intraarticular corticosteroid (CS) injections, arthrocentesis/aspiration, arthrotomy/incision and drainage, and arthroscopy were evaluated within 3 days post-HA. Results: Based on 694,404 HA injections, inflammation/infection rate was rare within 3 days of HA (up to 0.03%), with no statistical differences between hylan G-F 20 and non-hylan G-F 20 groups (matched by single or multiple injection products). The risk of knee arthrotomy/incision and drainage, arthroscopy, or arthrocentesis for hylan G-F 20 (2 mL) 3 weekly injection patients was lower than Hyalgan/Supartz and Orthovisc patients, but greater than Euflexxa patients. Overall, we found that Hylan G-F 20 (2 mL) 3 weekly injection had lower SALR rates compared to Hyalgan/Supartz and Orthovisc. However, Hylan G-F 20 (2 mL) 3 weekly injection had slightly higher rates of SALR when compared to Euflexxa. Among the single injection products, Hylan G-F 20 (6 mL) single injection had lower rates of SALR than Monovisc and Gel-One. Conclusions: This study shows no clear correlation between avian-derived or cross-linked products and SALR and provides evidence against avian-derived products or crosslinking as a source for these reactions.
Expanding the genetic spectrum of TUBB1-related thrombocytopenia
Authors: Palma-Barqueros Verónica , Bury Loredana , Kunishima Shinji , Lozano María Luisa , Rodríguez-Alen Augustín , Revilla Nuria , Bohdan Natalia , Padilla José , Fernández-Pérez María P. , de la Morena-Barrio María Eugenia , Marín-Quiles Ana , Benito Rocío , López-Fernández María F. , Marcellini Shally , Zamora-Cánovas Ana , Vicente Vicente , Martínez Constantino , Gresele Paolo , Bastida José M. , Rivera José 
Published: September 2021

Abstract
β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.
Dasatinib-based 2-step induction for adults with Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Sugiura Isamu , Doki Noriko , Hata Tomoko , Cho Ryuko , Ito Toshiro , Suehiro Youko , Tanaka Masatsugu , Kako Shinichi , Matsuda Mitsuhiro , Yokoyama Hisayuki , Ishikawa Yuichi , Taniguchi Yasuhiro , Hagihara Maki , Ozawa Yukiyasu , Ueda Yasunori , Hirano Daiki , Sakura Toru , Tsuji Masaaki , Kamae Tsuyoshi , Fujita Hiroyuki , Hiramoto Nobuhiro , Onoda Masahiro , Fujisawa Shin , Hatta Yoshihiro , Dobashi Nobuaki , Nishiwaki Satoshi , Atsuta Yoshiko , Kobayashi Yukio , Hayakawa Fumihiko , Ohtake Shigeki , Naoe Tomoki , Miyazaki Yasushi 
Published: September 2021

Abstract
The standard treatment for adults with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, ∼40% of patients cannot undergo HSCT in their first complete remission (CR1) because of chemotherapy-related toxicities or relapse before HSCT or older age. In this study, we evaluated dasatinib-based 2-step induction with the primary end point of 3-year event-free survival (EFS). The first induction (IND1) was dasatinib plus prednisolone to achieve CR, and IND2 was dasatinib plus intensive chemotherapy to achieve minimal residual disease (MRD) negativity. For patients who achieved CR and had an appropriate donor, HSCT during a consolidation phase later than the first consolidation, which included high-dose methotrexate, was recommended. Patients with pretransplantation MRD positivity were assigned to receive prophylactic dasatinib after HSCT. All 78 eligible patients achieved CR or incomplete CR after IND1, and 52.6% achieved MRD negativity after IND2. Nonrelapse mortality (NRM) was not reported. T315I mutation was detected in all 4 hematological relapses before HSCT. Fifty-eight patients (74.4%) underwent HSCT in CR1, and 44 (75.9%) had negative pretransplantation MRD. At a median follow-up of 4.0 years, 3-year EFS and overall survival were 66.2% (95% confidence interval [CI], 54.4-75.5) and 80.5% (95% CI, 69.7-87.7), respectively. The cumulative incidence of relapse and NRM at 3 years from enrollment were 26.1% and 7.8%, respectively. Dasatinib-based 2-step induction was demonstrated to improve 3-year EFS in Ph+ ALL. This study was registered in the UMIN Clinical Trial Registry as #UMIN000012173.
Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy
Authors: Bond David A. , Switchenko Jeffrey M. , Villa Diego , Maddocks Kami , Churnetski Michael , Gerrie Alina S. , Goyal Subir , Shanmugasundaram Krithika , Calzada Oscar , Kolla Bhaskar , Bachanova Veronika , Gerson James N. , Barta Stefan K. , Hill Brian T. , Sawalha Yazeed , Martin Peter , Maldonado Edward , Gordon Max , Danilov Alexey V. , Grover Natalie S. , Mathews Stephanie , Burkart Madelyn , Karmali Reem , Ghosh Nilanjan , Park Steven I. , Epperla Narendranath , Badar Talha , Guo Jin , Hamadani Mehdi , Fenske Timothy S. , Malecek Mary-Kate , Kahl Brad S. , Flowers Christopher R. , Blum Kristie A. , Cohen Jonathon B. 
Published: September 2021

Abstract
Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD&gt;24, defined as POD &gt;24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD&gt;24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD&gt;24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.
Canonical Wnt: a safeguard and threat for erythropoiesis
Authors: Krimpenfort Rosa A. , Nethe Micha 
Published: September 2021

Abstract
Myeloid dysplastic syndrome (MDS) reflects a preleukemic bone marrow (BM) disorder with limited treatment options and poor disease survival. As only a minority of MDS patients are eligible for curative hematopoietic stem cell transplantation, there is an urgent need to develop alternative treatment options. Chronic activation of Wnt/β-catenin has been implicated to underlie MDS formation and recently assigned to drive MDS transformation to acute myeloid leukemia. Wnt/β-catenin signaling therefore may harbor a pharmaceutical target to treat MDS and/or prevent leukemia formation. However, targeting the Wnt/β-catenin pathway will also affect healthy hematopoiesis in MDS patients. The control of Wnt/β-catenin in healthy hematopoiesis is poorly understood. Whereas Wnt/β-catenin is dispensable for steady-state erythropoiesis, its activity is essential for stress erythropoiesis in response to BM injury and anemia. Manipulation of Wnt/β-catenin signaling in MDS may therefore deregulate stress erythropoiesis and even increase anemia severity. Here, we provide a comprehensive overview of the most recent and established insights in the field to acquire more insight into the control of Wnt/β-catenin signaling in healthy and inefficient erythropoiesis as seen in MDS.
Correlation of active contact location with weight gain after subthalamic nucleus deep brain stimulation: a case series
Authors: Eguchi Katsuki , Shirai Shinichi , Matsushima Masaaki , Kano Takahiro , Yamazaki Kazuyoshi , Hamauchi Shuji , Sasamori Toru , Seki Toshitaka , Hirata Kenji , Kitagawa Mayumi , Otsuki Mika , Shiga Tohru , Houkin Kiyohiro , Sasaki Hidenao , Yabe Ichiro 
Published: September 2021

Abstract
Background
Weight gain (WG) is a frequently reported side effect of subthalamic deep brain stimulation; however, the underlying mechanisms remain unclear. The active contact locations influence the clinical outcomes of subthalamic deep brain stimulation, but it is unclear whether WG is directly associated with the active contact locations. We aimed to determine whether WG is associated with the subthalamic deep brain stimulation active contact locations.

Methods
We enrolled 14 patients with Parkinson’s disease who underwent bilateral subthalamic deep brain stimulation between 2013 and 2019. Bodyweight and body mass index were measured before and one year following the surgery. The Lead-DBS Matlab toolbox was used to determine the active contact locations based on magnetic resonance imaging and computed tomography. We also created sweet spot maps for WG using voxel-wise statistics, based on volume of tissue activation and the WG of each patient. Fluorodeoxyglucose-positron emission tomography data were also acquired before and one year following surgery, and statistical parametric mapping was used to evaluate changes in brain metabolism. We examined which brain regions’ metabolism fluctuation significantly correlated with increased body mass index scores and positron emission tomography data.

Results
One year after surgery, the body mass index increase was 2.03 kg/m2. The sweet spots for WG were bilateral, mainly located dorsally outside of the subthalamic nucleus (STN). Furthermore, WG was correlated with increased metabolism in the left limbic and associative regions, including the middle temporal gyrus, inferior frontal gyrus, and orbital gyrus.

Conclusions
Although the mechanisms underlying WG following subthalamic deep brain stimulation are possibly multifactorial, our findings suggest that dorsal stimulation outside of STN may lead to WG. The metabolic changes in limbic and associative cortical regions after STN-DBS may also be one of the mechanisms underlying WG. Further studies are warranted to confirm whether dorsal stimulation outside of STN changes the activities of these cortical regions.
Short-term effect of fine particulate matter and ozone on non-accidental mortality and respiratory mortality in Lishui district, China
Authors: Chen Yuqi , Jiao Zhigang , Chen Ping , Fan Lijun , Zhou Xudan , Pu Yuepu , Du Wei , Yin Lihong 
Published: September 2021

Abstract
Background
In recent years, air pollution has become an imminent problem in China. Few studies have investigated the impact of air pollution on the mortality of the middle-aged and elderly people. Therefore, this study aims to evaluate the impact of PM2.5 (fine particulate matter) and O3 (ozone) on non-accidental mortality and respiratory mortality of the middle-aged and elderly people in Lishui District of Nanjing and provide the evidence for potential prevention and control measures of air pollution.

Method
Using daily mortality and atmospheric monitoring data from 2015 to 2019, we applied a generalized additive model with time-series analysis to evaluate the association of PM2.5 and O3 exposure with daily non-accidental mortality and respiratory mortality in Lishui District. Using the population attributable fractions to estimate the death burden caused by short-term exposure to O3 and PM2.5。.

Result
For every 10 μg/m3 increase in PM2.5, non-accidental mortality increased 0.94% with 95% confidence interval (CI) between 0.05 and 1.83%, and PM2.5 had a more profound impact on females than males. For every 10 μg/m3 increase in O3, respiratory mortality increased 1.35% (95% CI: 0.05, 2.66%) and O3 had a more profound impact on males than females. Compared with the single pollutant model, impact of the two-pollutant model on non-accidental mortality and respiratory mortality slightly decreased. In summer and winter as opposed to the other seasons, O3 had a more obvious impact on non-accidental mortality. The population attributable fractions of non-accidental mortality were 0.84% (95% CI:0.00, 1.63%) for PM2.5 and respiratory mortality were 0.14% (95% CI:0.01, 0.26%) for O3. For every 10 μg/m3 decrease in PM2.5, 122 (95% CI: 6, 237) non-accidental deaths could be avoided. For every 10 μg/m3 decrease in O3, 10 (95% CI: 1, 38) respiratory deaths could be avoided.

Conclusion
PM2.5 and O3 could significantly increase the risk of non-accidental and respiratory mortality in the middle-aged and elderly people in Lishui District of Nanjing. Exposed to air pollutants, men were more susceptible to O3 damage, and women were more susceptible to PM2.5 damage. Reduction of PM2.5 and O3 concentration in the air may have the potential to avoid considerable loss of lives.
“We don’t want to sedate him” - A qualitative interview study on intentions when administering sedative drugs at the end of life in nursing homes and hospitals
Authors: Meesters Sophie , Grüne Bettina , Bausewein Claudia , Schildmann Eva 
Published: September 2021

AbstractBackgroundPrevious data indicate major differences between countries and settings regarding the intention when administering sedative drugs at the end of life and the perception, which drugs are sedating. Therefore, we aimed to explore the concept of ‘sedative drugs’ and the intentions of German healthcare professionals in general palliative care when administering sedative drugs at the end of life.MethodsSemi-structured qualitative interviews with physicians and nurses (n = 49). Recruitment took place via contact persons in five hospital departments (haematology/oncology (n = 2), neurology, geriatrics, gynaecology) and five nursing homes. We thematically analysed the transcripts by the Framework approach, using MAXQDA version 2018.2.ResultsMost interviewees referred to benzodiazepines, opioids, and antipsychotics. Some subsumed all into sedative drugs, others differentiated between sedative drugs, anxiolytics, and analgesics. In explaining their intention, interviewees particularly emphasized what they want to avoid when administering sedative drugs. We identified three main themes regarding (excluded) intentions: (1) use of sedative drugs to relieve the patient’s suffering with reduction of consciousness as side effect, (2) use of sedative drugs to relieve the situation for the team and/or the family, (3) distinction between intention and expectation regarding hastening death. Interviewees often equated the term ‘sedation’ with inducing a state of unconsciousness, which should be avoided.ConclusionGerman healthcare professionals in general palliative care seem to negatively connote the term ‘sedation’. Moreover, they see themselves in a more passive role by accepting a side effect rather than performing an intentional act. Critical reflection of indications and intentions in accordance with respective guidelines is needed.
Antimicrobial properties of tomato leaves, stems, and fruit and their relationship to chemical composition
Authors: Tam Christina C. , Nguyen Kevin , Nguyen Daniel , Hamada Sabrina , Kwon Okhun , Kuang Irene , Gong Steven , Escobar Sydney , Liu Max , Kim Jihwan , Hou Tiffany , Tam Justin , Cheng Luisa W. , Kim Jong H. , Land Kirkwood M. , Friedman Mendel 
Published: September 2021

Abstract
Background
We previously reported that the tomato glycoalkaloid tomatine inhibited the growth of Trichomonas vaginalis strain G3, Tritrichomonas foetus strain D1, and Tritrichomonas foetus-like strain C1 that cause disease in humans and farm and domesticated animals. The increasing prevalence of antibiotic resistance requires development of new tools to enhance or replace medicinal antibiotics.

Methods
Wild tomato plants were harvested and divided into leaves, stems, and fruit of different colors: green, yellow, and red. Samples were freeze dried and ground with a handheld mill. The resulting powders were evaluated for their potential anti-microbial effects on protozoan parasites, bacteria, and fungi. A concentration of 0.02% (w/v) was used for the inhibition of protozoan parasites. A high concentration of 10% (w/v) solution was tested for bacteria and fungi as an initial screen to evaluate potential anti-microbial activity and results using this high concentration limits its clinical relevance.

Results
Natural powders derived from various parts of tomato plants were all effective in inhibiting the growth of the three trichomonads to varying degrees. Test samples from leaves, stems, and immature ‘green’ tomato peels and fruit, all containing tomatine, were more effective as an inhibitor of the D1 strain than those prepared from yellow and red tomato peels which lack tomatine. Chlorogenic acid and quercetin glycosides were present in all parts of the plant and fruit, while caffeic acid was only found in the fruit peels. Any correlation between plant components and inhibition of the G3 and C1 strains was not apparent, although all the powders were variably effective. Tomato leaf was the most effective powder in all strains, and was also the highest in tomatine. S. enterica showed a minor susceptibility while B. cereus and C. albicans fungi both showed a significant growth inhibition with some of the test powders. The powders inhibited growth of the pathogens without affecting beneficial lactobacilli found in the normal flora of the vagina.

Conclusions
The results suggest that powders prepared from tomato leaves, stems, and green tomato peels and to a lesser extent from peels from yellow and red tomatoes offer potential multiple health benefits against infections caused by pathogenic protozoa, bacteria, and fungi, without affecting beneficial lactobacilli that also reside in the normal flora of the vagina.
Secondary cluster headache and numb chin syndrome as initial manifestation of high-grade B-lymphoma: a case report
Authors: Munoz-Cerón Joe , Díaz-Forero Felipe , Buitrago Adriana , Chinchilla Sandra 
Published: September 2021

Abstract
Background
Cluster headache is a primary condition characterized by severe headache accompanied by trigeminal autonomic signs. By definition, it is not attributed to underlying etiologies; however, under certain clinical characteristics, secondary etiologies must be ruled out.

Case presentation
We present the case of a 48-year-old Hispanic man with a history of episodic right orbital pain, lasting 30 minutes, associated with ipsilateral tearing, who prior to the onset of his symptoms reported loss of appetite, weight loss, and paresthesias in the right chin region. After work-up studies, high-grade lymphoma with infiltration to the right submental nerve was diagnosed, in which numb chin syndrome was the initial presentation. Despite initiation of treatment, the patient died 3 weeks after the diagnosis.

Conclusions
In the study of cluster headache, underlying etiologies must be considered when there are atypical clinical manifestations. Within these etiologies, metastases to pericranial nerves must be included, which, besides generating localized symptoms, can activate the trigeminal vascular system simulating headaches of primary etiology.