bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma
Authors: Panowski Siler H. , Kuo Tracy C. , Zhang Yi , Chen Amy , Geng Tao , Aschenbrenner Laura , Kamperschroer Cris , Pascua Edward , Chen Wei , Delaria Kathy , Farias Santiago , Bateman Marjorie , Dushin Russell G. , Chin Sherman M. , Van Blarcom Thomas J. , Yeung Yik Andy , Lindquist Kevin C. , Chunyk Allison G. , Kuang Bing , Han Bora , Mirsky Michael , Pardo Ingrid , Buetow Bernard , Martin Thomas G. , Wolf Jeffrey L. , Shelton David , Rajpal Arvind , Strop Pavel , Chaparro-Riggers Javier , Sasu Barbra J. 
Published: August 2019

AbstractThe restricted expression pattern of B-cell maturation antigen (BCMA) makes it an ideal tumor-associated antigen (TAA) for the treatment of myeloma. BCMA has been targeted by both CD3 bispecific antibody and antibody–drug conjugate (ADC) modalities, but a true comparison of modalities has yet to be performed. Here we utilized a single BCMA antibody to develop and characterize both a CD3 bispecific and 2 ADC formats (cleavable and noncleavable) and compared activity both in vitro and in vivo with the aim of generating an optimal therapeutic. Antibody affinity, but not epitope was influential in drug activity and hence a high-affinity BCMA antibody was selected. Both the bispecific and ADCs were potent in vitro and in vivo, causing dose-dependent cell killing of myeloma cell lines and tumor regression in orthotopic myeloma xenograft models. Primary patient cells were effectively lysed by both CD3 bispecific and ADCs, with the bispecific demonstrating improved potency, maximal cell killing, and consistency across patients. Safety was evaluated in cynomolgus monkey toxicity studies and both modalities were active based on on-target elimination of B lineage cells. Distinct nonclinical toxicity profiles were seen for the bispecific and ADC modalities. When taken together, results from this comparison of BCMA CD3 bispecific and ADC modalities suggest better efficacy and an improved toxicity profile might be achieved with the bispecific modality. This led to the advancement of a bispecific candidate into phase I clinical trials.
ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells
Authors: Jimenez-Pascual Ana , Hale James S. , Kordowski Anja , Pugh Jamie , Silver Daniel J. , Bayik Defne , Roversi Gustavo , Alban Tyler J. , Rao Shilpa , Chen Rui , McIntyre Thomas M. , Colombo Giorgio , Taraboletti Giulia , Holmberg Karl O. , Forsberg-Nilsson Karin , Lathia Justin D. , Siebzehnrubl Florian A. 
Published: August 2019

AbstractGlioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (GSC), but how GSCs maintain their stemness is incompletely understood and the subject of intense investigation. Here, we identify a novel signaling loop that induces and maintains GSCs consisting of an atypical metalloproteinase, ADAMDEC1, secreted by GSCs. ADAMDEC1 rapidly solubilizes FGF2 to stimulate FGFR1 expressed on GSCs. FGFR1 signaling induces upregulation of ZEB1 via ERK1/2 that regulates ADAMDEC1 expression through miR-203, creating a positive feedback loop. Genetic or pharmacologic targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signaling axis for GSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM.Significance:Cancer stem cells (CSC) drive tumor growth in many cancers including GBM. We identified a novel sheddase, ADAMDEC1, which initiates an FGF autocrine loop to promote stemness in CSCs. This loop can be targeted to reduce GBM growth.This article is highlighted in the In This Issue feature, p. 1469
МЕДСЕСТРИНСЬКІ НАУКОВІ ДОСЛІДЖЕННЯ В АВСТРІЇ
Authors: Palasyuk H. P. , Palasyuk B. M. 
Published: August 2019

Пріоритетним напрямом реформування системи підготовки сестринського персоналу в Австрії визначено впровадження вищої медсестринської освіти і подальший розвиток сестринської справи як науки. Наукові дослідження з проблем догляду за хворими виокремилися в окрему наукову спеціальність «Сестринствознавство». Предметом наукових досліджень у догляді за хворими є вивчення впливу захворювань і фізичних вад на життя людини і наукове обґрунтування найбільш доцільних форм медсестринської діяльності та медсестринських втручань у процесі догляду за хворими. Магістерська науково-дослідна робота повинна відповідати профілю магістратури, бути самостійною творчою роботою із вивчення актуальної проблеми медсестринства. Дисертація на здобуття наукового ступеня доктора наук з медсестринства – це незалежна дослідницька робота, яка вносить значний вклад у подальший розвиток медсестринської науки. На першому етапі написання докторської дисертації докторант самостійно або з допомогою наукового консультанта складає розгорнутий проект дисертаційного дослідження. На цьому етапі докторант на практичних заняттях отримує необхідну допомогу в плануванні дисертаційного дослідження. Матеріали планування докторської дисертації вивчає спеціально створена комісія. Докторанти повинні брати активну участь у конференціях, у тому числі і щорічних Європейських докторських конференціях з проблем догляду за хворими. Науково-дослідні роботи виконуються в руслі наукової роботи інституту, в якому навчається докторант. Основні положення дисертації висвітлюються у щонайменше чотирьох одноосібних публікаціях у провідних наукових журналах. Дисертація складається зі вступу, опису методики і отриманих результатів проведеного дослідження, основної частини, у якій викладені основні положення дисертаційного дослідження, і висновків. Текст дисертації повинен бути написаний англійською мовою, висновки – англійською і німецькою мовами.
Наукові дослідження у медсестринстві Австрії сприяють формуванню наукового підґрунтя для медичної практики працівників середньої ланки, забезпечують науковий підхід до сестринської діяльності на засадах доказової медицини.
Catheter Ablation Versus Medical Therapy for Atrial Fibrillation
Authors: Asad Zain Ul Abideen , Yousif Ali , Khan Muhammad Shahzeb , Al-Khatib Sana M. , Stavrakis Stavros 
Published: August 2019

Background:
Despite the publication of several randomized clinical trials comparing catheter ablation (CA) with medical therapy (MT) in patients with atrial fibrillation (AF), the superiority of one strategy over another is still questioned by many. In this meta-analysis of randomized controlled trials, we compared the efficacy and safety of CA with MT for AF.

Methods:
We systematically searched MEDLINE, EMBASE, and other online sources for randomized controlled trials of AF patients that compared CA with MT. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular hospitalizations and recurrence of atrial arrhythmia. Subgroup analyses stratified by the presence of heart failure with reduced ejection fraction, type of AF, age, and sex were performed. Risk ratios (RRs) with 95% CIs were calculated using a random effects model, and Mantel-Haenszel method was used to pool RR.

Results:

Eighteen randomized controlled trials comprising 4464 patients (CA, n=2286; MT, n=2178) were included. CA resulted in a significant reduction in all-cause mortality (RR, 0.69; 95% CI, 0.54–0.88;
P
=0.003) that was driven by patients with AF and heart failure with reduced ejection fraction (RR, 0.52; 95% CI, 0.35–0.76;
P
=0.0009). CA resulted in significantly fewer cardiovascular hospitalizations (hazard ratio, 0.56; 95% CI, 0.39–0.81;
P
=0.002) and fewer recurrences of atrial arrhythmias (RR, 0.42; 95% CI, 0.33–0.53;
P
<0.00001). Subgroup analyses suggested that younger patients (age, <65 years) and men derived more benefit from CA compared with MT.

Conclusions:
CA is associated with all-cause mortality benefit, that is driven by patients with AF and heart failure with reduced ejection fraction. CA reduces cardiovascular hospitalizations and recurrences of atrial arrhythmia for patients with AF. Younger patients and men appear to derive more benefit from CA.
Assessment of the 2017 AHA/ACC/HRS Guideline Recommendations for Implantable Cardioverter-Defibrillator Implantation in Cardiac Sarcoidosis
Authors: Kazmirczak Felipe , Chen Ko-Hsuan Amy , Adabag Selcuk , von Wald Lisa , Roukoz Henri , Benditt David G. , Okasha Osama , Farzaneh-Far Afshin , Markowitz Jeremy , Nijjar Prabhjot S. , Velangi Pratik S. , Bhargava Maneesh , Perlman David , Duval Sue , Akçakaya Mehmet , Shenoy Chetan 
Published: August 2019

Background:
Implantable cardioverter-defibrillators are used to prevent sudden cardiac death in patients with cardiac sarcoidosis. The most recent recommendations for implantable cardioverter-defibrillator implantation in these patients are in the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. These recommendations, based on observational studies or expert opinion, have not been assessed. We aimed to assess them.

Methods:
We performed a large retrospective cohort study of patients with biopsy-proven sarcoidosis and known or suspected cardiac sarcoidosis that underwent cardiovascular magnetic resonance imaging. Patients were followed for a composite end point of significant ventricular arrhythmia or sudden cardiac death. The discriminatory performance of the Guideline recommendations was tested using time-dependent receiver operating characteristic analyses. The optimal cutoff for the extent of late gadolinium enhancement predictive of the composite end point was determined using the Youden index.

Results:
In 290 patients, the class I and IIa recommendations identified all patients who experienced the composite end point during a median follow-up of 3.0 years. Patients meeting class I recommendations had a significantly higher incidence of the composite end point than those meeting class IIa recommendations. Left ventricular ejection fraction (LVEF) >35% with >5.7% late gadolinium enhancement on cardiovascular magnetic resonance imaging was as sensitive as and significantly more specific than LVEF >35% with any late gadolinium enhancement. Patients meeting 2 class IIa recommendations, LVEF >35% with the need for a permanent pacemaker and LVEF >35% with late gadolinium enhancement >5.7%, had high annualized event rates. Excluding 2 class IIa recommendations, LVEF >35% with syncope and LVEF >35% with inducible ventricular arrhythmia, resulted in improved discrimination for the composite end point.

Conclusions:
We assessed the Guideline recommendations for implantable cardioverter-defibrillator implantation in patients with known or suspected cardiac sarcoidosis and identified topics for future research.
Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex‐Specific Criteria
Authors: Ferry Amy V. , Anand Atul , Strachan Fiona E. , Mooney Leanne , Stewart Stacey D. , Marshall Lucy , Chapman Andrew R. , Lee Kuan Ken , Jones Simon , Orme Katherine , Shah Anoop S. V. , Mills Nicholas L. 
Published: August 2019

Background
Sex‐specific criteria are recommended for the diagnosis of myocardial infarction, but the impact of these on presenting characteristics is unknown.

Methods and Results

We evaluated patient‐reported symptoms in 1941 patients (39% women) with suspected acute coronary syndrome attending the emergency department in a substudy of a prospective trial. Standardized criteria defined typical and atypical presentations based on pain nature, location, radiation, and additional symptoms. Diagnosis of myocardial infarction was adjudicated using a high‐sensitivity cardiac troponin I assay with sex‐specific thresholds (>16 ng/L women, >34 ng/L men). Patients identified who were missed by the contemporary assay with a uniform threshold (≥50 ng/L) were reclassified by this approach. Type 1 myocardial infarction was diagnosed in 16% (184/1185) of men and 12% (90/756) of women, with 9 (5%) men and 27 (30%) women reclassified using high‐sensitivity cardiac troponin I and sex‐specific thresholds. Chest pain was the presenting symptom in 91% (1081/1185) of men and 92% (698/756) of women. Typical symptoms were more common in women than in men with myocardial infarction (77% [69/90] versus 59% [109/184];
P
=0.007), and differences were similar in those reclassified (74% [20/27] versus 44% [4/9];
P
=0.22). The presence of ≥3 typical features was associated with a positive likelihood ratio for the diagnosis of myocardial infarction in women (positive likelihood ratio, 1.18; 95%
CI
, 1.03–1.31) but not in men (positive likelihood ratio 1.09; 95%
CI
, 0.96–1.24).

Conclusions
Typical symptoms are more common and have greater predictive value in women than in men with myocardial infarction whether or not they are diagnosed using sex‐specific criteria.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier
NCT
01852123.
Predicting spatial and temporal effects of climate change on the South American lizard genus Teius (Squamata: Teiidae)
Authors: Minoli Ignacio , Cacciali Pier , Morando Mariana , Avila Luciano Javier 
Published: August 2019

Abstract
The consequences of past or future climate change have been studied in many physical and biological systems, and their effects could change the ecology and spatial distribution of suitable areas for a wide variety of organisms. We analyzed the environmental and geographic space of the current suitable area projecting these conditions into Mid-Holocene and 2050 RCP8.5 scenarios to quantify whether climate change would affect the distribution and size of environmental and geographic space for lizard species of the genus Teius. The potentially suitable geographic area for the Mid-Holocene was found to be smaller than today for T. oculatus (−29.55%) and for T. teyou (−6.82%), but for T. suquiensis it was inferred as a larger suitable area (+26%). For the future scenario all species showed a decrease in the potentially suitable area compared to the present (T. oculatus = − 9.30%, T. teyou = − 0.79%, T. suquiensis = − 37.58%). The PCA axes that in the environmental space showed a higher contribution for PC1-2 in Mid-Holocene and Present were mostly related to temperature and for PC3 with altitude variables, for the 2050 scenario were temperature for PC1, precipitation for PC2 and altitude-temperature for PC3. The current Teius’ potentially suitable geographic space results versus the other temporal forecasts, showed specific differences in magnitude changes. This work illustrates how ectothermic organisms might have to face major changes in their environmental and geographic space as a consequence of the effect of climate changes.
Two new earthworm species of the genus Amynthas (Oligochaeta: Megascolecidae) from central Taiwan, with comments on some recent species assignments in Amynthas and Metaphire
Authors: SHEN HUEI-PING , CHANG CHIH-HAN , CHIH WEN-JAY 
Published: August 2019

This study describes two new species of earthworms belonging to the genus Amynthas (Oligochaeta: Megascolecidae) from central Taiwan. They are named Amynthas luridus sp. nov. and Amynthas ruiyenensis sp. nov. Both species are octothecal with the former found at elevations of 1500–2300 m and the latter at an elevation of 2200 m from the Central Mountain Range. In addition, DNA barcodes are made available for the first time for the following species: Amynthas catenus Tsai et al., 2001, Amynthas exiguus aquilonius Tsai et al., 2001, Amynthas proasacceus Tsai et al., 2001, Amynthas hohuanmontis Tsai et al., 2002, Amynthas tessellatus Shen et al., 2002, Amynthas fenestrus Shen et al., 2003, Amynthas tantulus Shen et al., 2003, and Amynthas uvaglandularis Shen et al., 2003. Furthermore, Amynthas exiguus ssp. aquilonius Tsai et al., 2001 distributed at elevations of 2200–3000 m in the Central Mountain Range is elevated to species level, as A. aquilonius Tsai et al., 2001. The highest altitude record so far for the exotic Eukerria saltensis (Beddard, 1895) in Taiwan, 2200 m above sea level, is documented. Moreover, some recent assignments of species to Amynthas and Metaphire and synonymies of names are critically discussed. It is argued that idiosyncratic genus concepts, inadequate species comparisons, and unexplained synonymies should be avoided. A hitherto undetected and possibly monophyletic species group of mainly Korean Amynthas species in the A. tokioensis-group is indicated, characterized by numerous genital papillae around each spermathecal pore and male porophore, large ampullae, long diverticula, large prostate glands, and manicate intestinal caeca. The names A. bimaculata, A. silvatica and A. surcata (Ishizuka, 1999), as well as A. odaesanensis, A. righii, A. fasciiformis, and A. sanchongensis Hong & James, 2001, previously declared as junior synonyms of A. tappensis (Ohfuchi, 1935), are revalidated.
A revision of the concept of Mago O. Pickard-Cambridge, 1882, and proposal of a new genus (Araneae: Salticidae: Amycini)
Authors: RUIZ GUSTAVO R.S. , MADDISON WAYNE P. , GALIANO MARIA ELENA 
Published: August 2019

In this paper we redescribe the type species of Mago O. Pickard-Cambridge, M. intentus O. Pickard-Cambridge, and describe Mago brimodes Ruiz & Maddison sp. nov. from Ecuador. Based on both morphological features and the 16SND1 gene region, we concluded that the larger spiders traditionally identified as Mago, such as Mago acutidens Simon and related species, are not closely related to the small dark M. intentus (type species) and M. brimodes. Matinta Ruiz & Maddison gen. nov. is therefore proposed to hold most species previously included in Mago. The following species are transferred from Mago to the new genus: Matinta acutidens (Simon, 1900) comb. nov. (type species), Matinta apophysis (Costa & Ruiz, 2017) comb. nov., Matinta balbina (Patello & Ruiz, 2014) comb. nov., Matinta chickeringi (Caporiacco, 1954) comb. nov., Matinta delicata (Patello & Ruiz, 2014) comb. nov., Matinta fasciata (Mello-Leitão, 1940) comb. nov., Matinta fonsecai (Soares & Camargo, 1948) comb. nov., Matinta furcata (Costa & Ruiz, 2017) comb. nov., Matinta jurutiensis (Patello & Ruiz, 2014) comb. nov., Matinta longidens (Simon, 1900) comb. nov., Matinta mimica (Costa & Ruiz, 2017) comb. nov., Matinta opiparis (Simon, 1900) comb. nov., Matinta pardo (Costa & Ruiz, 2017) comb. nov., Matinta procax (Simon, 1900) comb. nov., Matinta saperda (Simon, 1900) comb. nov., Matinta silvae (Crane, 1943) comb. nov., Matinta similis (Patello & Ruiz, 2014) comb. nov., Matinta steindachneri (Taczanowski, 1878) comb. nov. and Matinta vicana (Simon, 1900) comb. nov. Mago dentichelis Crane, 1949 is transferred to Noegus Simon.
Successful whole-blood exchange transfusion in a patient with paroxysmal nocturnal hemoglobinuria: A case report and literature review
Authors: Zhang Zhimin , Shen Yamei , Shu Xiangwu , Li Bijuan , Li Ning 
Published: August 2019

Objective Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of the hematopoietic stem cells that involves all blood cells. The primary aim of this study was to assess the role of whole-blood exchange (WBE) in treating patients with PNH. Methods A 32-year-old male patient was admitted our hospital because of severe anemia. His clinical test results indicated serious hemolysis, with positive anti-I on pretransfusion antibody screening tests. Because immunosuppressive therapy was ineffective and red blood cell (RBC) transfusion may aggravate hemolytic symptoms, the COBE Spectra blood cell separator was used for WBE. Results We performed WBE, where 1789 mL of the patient’s blood was removed and replaced with 12 U of packed RBCs, along with 150 mL of frozen plasma and 200 mL of normal saline (total volume, 1883 mL), representing an exchange of 42.5% of the patient’s total blood volume (approximately 4209 mL). The WBE treatment was considered successful. Rapid improvement in clinical signs and symptoms were observed after the WBE transfusion. The patient was discharged from the hospital on the third day after treatment. Conclusion Whole-blood exchange may be an applicable emergency treatment for rescuing PNH patients with severe or life-threatening hemolysis.
Outcomes of fertility-sparing surgery for stage II and III serous borderline ovarian tumors
Authors: Lu Ziyang , Li Bin , Gu Chao 
Published: August 2019

Objective This study was performed to assess the feasibility of conservative treatment for stage II or III serous borderline ovarian tumors (BOTs). Methods Twenty-one patients were treated conservatively for advanced serous BOTs from 2006 to 2017. Two patients were lost to follow-up. The patients’ clinical status, surgical results, fertility results, and oncological outcomes were collected. Results The patients’ median age at surgery was 28 years (range, 22–37 years). The median follow-up interval was 74 months (range, 16–214 months). Among the 19 patients who were followed up, 8 had stage II tumors and 11 had stage III tumors. Sixteen patients had noninvasive peritoneal implants. Two patients developed tumor metastasis to the fallopian tubes and one developed metastasis to the pelvic lymph nodes and omentum. The total recurrence rate was 26.3%. Seventeen (89.5%) patients were nulliparous. Four of 10 patients who wished to preserve their fertility obtained natural pregnancy. No patients died of their disease. Conclusions This study supports the efficacy of conservative treatment for advanced BOTs with respect to its favorable fertility result. The overall prognosis is not changed by conservative treatment.
Moderate hypofractionated helical tomotherapy for localized prostate cancer: preliminary report of an observational prospective study
Authors: Cuccia Francesco , Mazzola Rosario , Arcangeli Stefano , Mortellaro Gianluca , Figlia Vanessa , Caminiti Giovanni , Di Paola Gioacchino , Spera Antonio , Iacoviello Giuseppina , Alongi Filippo , Lo Casto Antonio , Magrini Stefano Maria , Ferrera Giuseppe 
Published: August 2019

Objective: To report preliminary findings of a phase II study exploring the clinical outcomes of moderate hypofractionated radiotherapy performed with helical tomotherapy (HT) using computed tomography–magnetic resonance imaging–based planning for localized prostate cancer. Methods: The phase II prospective study received ethics approval from our institutional ethics committee. A dose of 60 Gy/20 fractions for low–intermediate risk prostate cancer by means of HT was explored. Primary endpoints of the study were acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. Secondary endpoints were quality of life and biochemical-free survival. Results: A total of 35 patients were included in this interim report. At the time of the analysis, median follow-up was 36 months (range, 13–62). Acute GI toxicity was recorded as follows: grade 1 in 34% and grade 2 in 14%; acute GU toxicity was grade 1 in 71% and grade 2 in 11%. For the entire population of the study, no acute toxicities ⩾ grade 3 occurred. A single case of late grade 3 GU toxicity was registered, whereas no late GI toxicity ⩾grade 3 was recorded. At the time of the final assessment, no biochemical failure was detected. Conclusions: The preliminary results of the present phase II trial, using HT for moderate hypofractionation in localized prostate cancer, are optimal. In fact, HT guaranteed an acceptable tolerability profile with low rates of GU and GI side effects and, more specifically, no acute severe adverse events were recorded. Long-term findings are warranted.