tbuckley/cabot-search huggingface dataset:
Treatment of hereditary hypotrichosis simplex of the scalp with topical gentamicin
Authors: A. Peled, L. Samuelov, O. Sarig, R. Bochner, L. Malki, M. Pavlovsky, E. Pichinuk, M. Weil, E. Sprecher
Journal: British Journal of Dermatology (2019)

Hypotrichosis simplex of the scalp (HSS) is characterized by progressive loss of scalp hair that results in almost complete baldness at a young age. HSS is often caused by dominant nonsense mutations in CDSN encoding corneodesmosin, leading to the formation of an amyloid‐like material, which interferes with normal hair follicle cycle. As gentamicin has been shown to mediate ribosomal read‐through, we aimed to ascertain its therapeutic efficacy in a small series of patients carrying a recurrent mutation in CDSN . We used a green fluorescence reporter assay system, confocal microscopy and Western blot analysis to ascertain in vitro the ability of gentamicin to induce translational read‐through across a causative CDSN mutation. Using a reporter assay, we initially showed that gentamicin induces read‐through activity across an HSS‐causing nonsense mutation. Gentamicin was further shown to rescue corneodesmosin translation in primary keratinocytes obtained from a patient with HSS. To validate the in vitro data, we conducted a pilot clinical trial where the scalp of four patients was treated topically with gentamicin for 6 months, demonstrating significant improvement as ascertained by the Severity of Alopecia Tool score. Our findings indicate that topical gentamicin should be considered as a potential therapeutic modality in HSS. What's already known about this topic? Hypotrichosis simplex of the scalp (HSS) is caused by nonsense mutations in CDSN encoding corneodesmosin. The mutant corneodesmosin has been hypothesized to be toxic to the hair follicles, leading to hypotrichosis. Disorders caused by nonsense mutations are amenable to ribosomal read‐through using gentamicin. What does this study add? Gentamicin enhanced read‐through activity and promoted full‐length corneodesmosin synthesis in primary keratinocytes derived from patients carrying a nonsense mutation in CDSN. Topical treatment with gentamicin was found to rescue the hypotrichosis phenotype partially in four patients with HSS. What is the translational message? Topical gentamicin should be considered as a potential treatment for HSS. Linked Comment:Kibbi and Rajan. Br J Dermatol 2020; 183:11.
Phase Ib Study of the Anti-TIM-3 Antibody MBG453 in Combination with Decitabine in Patients with High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
Authors: Uma Borate, Jordi Esteve, Kimmo Porkka, Steve Knapper, Norbert Vey, Sebastian Scholl, Guillermo Garcia-Manero, Martin Wermke, Jeroen Janssen, Elie Traer, Chong Chyn Chua, Rupa Narayan, Natalia Tovar, Mika Kontro, Oliver Ottmann, Haiying Sun, Tyler Longmire, Sebastian Szpakowski, Serena Liao, Anuradha Patel, Mikael L Rinne, Andrew Brunner, Andrew H. Wei
Journal: Blood (2019)
Genome Sequencing during a Patient’s Journey through Cancer
Authors: Jyoti Nangalia, Peter J Campbell
Journal: New England Journal of Medicine (2019)

Interview with Dr. Peter J. Campbell on genome sequencing in cancer. (12:43)Download Breakthroughs in gene-sequencing methods and bioinformatics have ushered in a new era in cancer diagnosis and management. Powerful analytic tools are beginning to improve cancer nosology and facilitate the discovery of genetic defects in tumor cells that can be exploited for treatment and the monitoring of disease regression and progression. This article is accompanied by an explanatory video, an illustrated glossary, and an audio interview with the author.
Hematopoietic stem cell function in β-thalassemia is impaired and is rescued by targeting the bone marrow niche
Authors: Annamaria Aprile, Alessandro Gulino, Mariangela Storto, Isabella Villa, Stefano Beretta, Ivan Merelli, Alessandro Rubinacci, Maurilio Ponzoni, Sarah Marktel, Claudio Tripodo, Maria Rosa Lidonnici, Giuliana Ferrari
Journal: Blood (2020)
Considerations and Methods for Placebo Controls in Surgical Trials: State of the Art Review and ASPIRE Guidance
Authors: D J Beard, M K Campbell, J M Blazeby, A J Carr, C Weijer, B Cuthbertson, R Buchbinder, T Pinkney, F Bishop, J Pugh, S Cousins, I Harris, S Lohmander, N Blencowe, K Gillies, P Probst, C Brennan, A Cook, D Farrah-Hockley, J Savulescu, R Huxtable, A Rangan, I Tracey, P Brocklehurst, M Ferreira, J Nicholl, B Reeves, F Hamdy, S Rowley, J A Cook
Journal: The Lancet (2019)
A claim for cognitive history
Authors: Henry M Cowles, Jamie Kreiner
Journal: Behavioral and Brain Sciences (2019)

Abstract History is a potential tool for cognitive scientists interested in metacognitive categories like “creativity” and “innovation.” As a way of thinking, history suggests alternative accounts of the development of innovation and growth, for example. Life History Theory is one such account, but its roots in the Industrial Revolution make it a problematic tool for telling the history of that period.
Discovery of novel protein biomarkers in formalin fixed paraffin embedded endometrial cancer tissue by mass spectrometry
Authors: David Krizman, Marlene Darfler, Jill Ray, Mark Stoler, Attila Lorincz
Journal: Cancer Research (2008)

3971  Endometrial cancer is the most common cancer of the female reproductive system found in the US. If the cancer is detected early, a large percentage of patients survive at least five years. A study was undertaken to identify candidate protein biomarkers for early detection of endometrial cancer using formalin fixed paraffin embedded tissue samples. A collection of well documented formalin fixed endometrial tissues was assembled and microdissected utilizing the Director™ laser microdissection technology to collect both early stage cancerous epithelium and normal epithelium. Tissue lysates were prepared from the microdissected cells utilizing the Liquid Tissue® reagents and protocol. Global proteomic analysis was performed by high resolution tandem mass spectrometry yielding high confidence analysis of >30,000 unique peptides and >13,000 unique proteins across the entire dataset. Quantitative differential protein expression between normal endometrial epithelium and early stage cancerous epithelium was determined by the spectral count method. Numerous candidate protein biomarkers with potential for use in screening for early stage endometrial cancer were identified. The biomarkers identified are amenable to analysis of surgical specimens, biopsied material, and/or bodily fluids. A selection of the proteins from this dataset are being further verified and validated for their potential use as biomarkers. The combination of proteomic technologies used in this study allows for quantitative protein biomarker analysis which can be applied to both discovery and validation of proteins directly in a collection of well characterized and annotated formalin fixed endometrial tissue.
Authors’ reply to McKenna-Barry and Ryan
Authors: Naveed Sattar, William Alazawi
Journal: BMJ (2019)

We thank McKenna-Barry and Ryan for their interest in our article on non-alcoholic fatty liver disease and cardiovascular risk.12 Although studies have reported associations between stage of liver disease and surrogate markers of cardiovascular disease, we agree that more work is needed to examine whether the existence or stage of non-alcoholic steatohepatitis is a meaningful independent risk factor for …
Mature T-/NK-cell lymphomas: Prognostic factors and treatment outcome of patients treated on studies of the German High-Grade Lymphoma Study Group (DSHNHL)
Authors: N. Schmitz, M. Ziepert, M. Nickelsen, S. P. Wolf, L. Truemper, M. Loeffler, A. Ho, B. Metzner, A. Rosenwald, M. Pfreundschuh
Journal: Journal of Clinical Oncology (2009)

8564 Background: T-cell lymphomas represent a heterogeneous group of malignancies difficult to diagnose and to treat. We evaluated patients (pts) diagnosed according to WHO standards and treated on prospective studies of the DSHNHL. Chemotherapy regimens (CHOP-14 and CHOEP) had significantly improved outcomes of patients with aggressive B-NHL. Methods: Between 1993 and 2006 we treated 329 pts with ALK-positive ALCL (73 pts), ALK-negative ALCL (108 pts), PTCL, NOS (68 pts), AITL (28 pts), NK-/T-cell lymphoma (18 pts), and rare T-cell lymphomas on prospective studies. All pts received CHOP ± etoposide (E) every 2 or 3 weeks; in pts &lt;=60 yrs C, H, and E were escalated to further improve outcomes. Results: The majority of pts with ALK-positive ALCL presented with IPI 0, 1 (62%) or IPI 2 (26%) and had an excellent overall survival (OS) of 89 % and event-free survival (EFS) of 75% at 3 yrs. E significantly improved TTTF for pts &lt;=60 yrs (p=0.007). Pts with other histologies did significantly worse (OS 58%, EFS 44 % at 3 yrs). The IPI discriminated between pts with a favorable (IPI 0, 1: OS 73%), moderate (IPI 2: OS 55%), and poor prognosis (IPI 3: OS 35%; IPI 4, 5: OS 19%) at 3 yrs. OS, EFS were significantly better for ALK-positive ALCL but did not significantly differ for pts in other histological subgroups. Neither shortening of the treatment interval (CHOP-14) nor the addition of E (CHOEP-21 or -14) significantly improved outcome of elderly pts. In younger pts (ALK-positive ALCL were excluded) and good-risk disease (LDH &lt;= N) there was a trend for better EFS after the addition of E to CHOP (EFS 63% vs. 48%, p = 0.065). The MegaCHOEP protocol (Schmitz et al., CANCER 2006) failed to improve treatment results for younger pts with poor-risk disease (EFS at 3 yrs: 25.9%, 95% CI: 10.4–41.4); the prospective study comparing MegaCHOEP with CHOEP-14 was stopped for pts with T-cell lymphoma. Conclusions: CHO(E)P results in excellent OS of pts with ALK-positive ALCL and selected pts with other histologies and low IPI. All other pts did poorly; CHOP-14 or the addition of E failed to significantly improve outcomes. Notably, also the MegaCHOEP protocol characterized by repetitive high-dose therapy and ASCT did not result in significant improvement. No significant financial relationships to disclose.
Is “the brain” a helpful metaphor for neuroscience?
Authors: Fred Keijzer
Journal: Behavioral and Brain Sciences (2019)

Abstract Brette criticizes the notion of neural coding as used in neuroscience as a way to clarify the causal structure of the brain. This criticism will be positioned in a wider range of findings and ideas from other branches of neuroscience and biology. While supporting Brette's critique, these findings also suggest the need for more radical changes in neuroscience than Brette envisions.
Treatment with pralsetinib (formerly BLU-667), a potent and selective RET inhibitor, provides rapid clearance of ctDNA in patients with RET-altered non-small cell lung cancer (NSCLC) and medullary thyroid cancer (MTC)
Authors: D.H. Lee, V. Subbiah, J.F. Gainor, M.H. Taylor, V.W. Zhu, R.C. Doebele, G. Lopes, C. Baik, E. Garralda, S.M. Gadgeel, D.-W. Kim, C.D. Turner, M. Palmer, S. Miller, G. Curigliano
Journal: Annals of Oncology (2019)
Long-term efficacy of low-dose radiation therapy on symptoms in patients with knee and hand osteoarthritis: follow-up results of two parallel randomised, sham-controlled trials
Authors: Cornelia H M van den Ende, Michiel J M Minten, Mathilde M Leseman-Hoogenboom, Frank H J van den Hoogen, Alfons A den Broeder, Elien A M Mahler, Philip M P Poortmans
Journal: The Lancet Rheumatology (2019)
Interim Analysis of a Phase II Study of the Glutaminase Inhibitor Telaglenastat (CB-839) in Combination with Azacitidine in Advanced Myelodysplastic Syndrome (MDS)
Authors: Veronica A Guerra, Jan A. Burger, Gautam M. Borthakur, Elias Jabbour, Naveen Pemmaraju, Tapan M. Kadia, Guillermo Garcia-Manero, Hagop M. Kantarjian, Marina Y Konopleva, Courtney D. DiNardo
Journal: Blood (2019)
Eligibility and Radiologic Assessment for Adjuvant Clinical Trials in Kidney Cancer
Authors: Sundeep Agrawal, Naomi B. Haas, Mohammadhadi Bagheri, Brian R. Lane, Jonathan Coleman, Hans Hammers, Gennady Bratslavsky, Cynthia Chauhan, Lauren Kim, Venkatesh P. Krishnasamy, Jamie Marko, Virginia Ellen Maher, Amna Ibrahim, Frank Cross, Ke Liu, Julia A. Beaver, Richard Pazdur, Gideon M. Blumenthal, Harpreet Singh, Elizabeth R. Plimack, Toni K. Choueiri, Robert Uzzo, Andrea B. Apolo
Journal: JAMA Oncology (2019)

To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC).On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, radiologists, and patient advocates, convened at a public workshop to discuss eligibility for trial entry and radiologic criteria for assessing disease recurrence in adjuvant trials in RCC. Multiple virtual meetings were conducted to address the issues identified at the workshop.The key workshop conclusions for adjuvant RCC therapy clinical trials were as follows. First, patients with non-clear cell RCC could be routinely included, preferably in an independent cohort. Second, patients with T3-4, N+M0, and microscopic R1 RCC tumors may gain the greatest advantages from adjuvant therapy. Third, trials of agents not excreted by the kidney should not exclude patients with severe renal insufficiency. Fourth, therapy can begin 4 to 16 weeks after the surgical procedure. Fifth, patients undergoing radical or partial nephrectomy should be equally eligible. Sixth, patients with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials. Seventh, all suspicious regional lymph nodes should be fully resected. Eighth, computed tomography should be performed within 4 weeks before trial enrollment; for patients with renal insufficiency who cannot undergo computed tomography with contrast, noncontrast chest computed tomography and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be performed. Ninth, when feasible, biopsy should be undertaken to identify any malignant disease. Tenth, when biopsy is not feasible, a uniform approach should be used to evaluate indeterminate radiologic findings to identify what constitutes no evidence of disease at trial entry and what constitutes radiologic evidence of disease. Eleventh, a uniform approach for establishing the date of recurrence should be included in any trial design. Twelfth, patient perspectives on the use of placebo, conditions for unblinding, and research biopsies should be considered carefully during the conduct of an adjuvant trial.The discussions suggested that a uniform approach to eligibility criteria and radiologic disease assessment will lead to more consistently interpretable trial results in the adjuvant RCC therapy setting.
Phase 2 Study of Tirabrutinib (ONO/GS-4059), a Second-Generation Bruton's Tyrosine Kinase Inhibitor, Monotherapy in Patients with Treatment-Naïve or Relapsed/Refractory Waldenström Macroglobulinemia
Authors: Wataru Munakata, Naohiro Sekiguchi, Rai Shinya, Kenshi Suzuki, Hiroshi Handa, Hirohiko Shibayama, Tomoyuki Endo, Yasuhito Terui, Noriko Iwaki, Noriko Fukuhara, Hiro Tatetsu, Shinsuke Iida, Takayuki Ishikawa, Ryota Shiibashi, Koji Izutsu
Journal: Blood (2019)
Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy
Authors: Dandan Wan, Yiliang Yang, Yiyao Liu, Xingli Cun, Man Li, Shanshan Xu, Wei Zhao, Yangyang Xiang, Yue Qiu, Qianwen Yu, Xian Tang, Zhirong Zhang, Qin He
Journal: Journal of Controlled Release (2019)
Differential serum protein expression in pancreatic cancer patients using two dimensional-differential gel electrophoresis.
Authors: Kenneth H. Yu, Anil K. Rustgi, Ian A. Blair
Journal: Cancer Research (2004)

3545  The purpose of this study is to develop techniques for identifying cancer biomarkers in human serum using differential in-gel electrophoresis (DIGE), and characterizing the protein biomarkers using mass spectrometry (MS). A major problem in profiling protein expression by DIGE comes from the presence of high concentrations of a small number of proteins. This makes it difficult to run gels reproducibly as well as masking differential protein expression of proteins with similar properties or those which non-covalently bind to the abundant proteins. Therefore, samples were first chromatographed using a multi-affinity HPLC column (Agilent Technologies), in order to selectively remove albumin, immunoglobulins, transferrin, haptoglobin, and antitrypsin from the serum. This system was used to process multiple samples of normal human serum. The low abundance protein fraction was collected for each sample. Fifty micrograms of each sample were covalently labeled with one of three size and charge-matched spectrally resolvable CyDye fluors (Amersham Biosciences). Samples were mixed, separated by 2-D gel electrophoresis, and analyzed using DeCyder Differential Analysis Software. On average, only 6.1% of all protein spots demonstrated greater than 2-fold variation between samples. Serum samples from three individuals with pancreatic cancer and three individuals without cancer were then compared. A pooled sample containing serum from all six individuals was created. Serum samples were processed using the multi-affinity column. The cancer, control, and pooled samples were labeled with Cy3, Cy5, or Cy2, respectively. Samples were mixed, separated by 2-D gel electrophoresis, and analyzed using DeCyder Differential Analysis Software. An average of 144 different protein spots had Cy3/Cy5 ratios greater than 2, while 106 protein spots had Cy3/Cy5 ratios less than 0.5. These preliminary results suggest that affinity column enrichment and 2-D DIGE can be used to identify numerous proteins differentially expressed in serum from individuals with pancreatic cancer. Further analyses to determine which protein spots are differentially expressed in all cancer serum samples, and to identify these proteins by matrix-assisted laser desorption –time-of-flight/MS and tandem MS (MS/MS) and liquid chromatography (LC)/MS/MS are currently underway. Supported by NIH grant P30 CA16520 and NIH/NIDDK grant P32-DK-007066-29.
Vitamin D and Calcium for the Prevention of Fracture
Authors: Pang Yao, Derrick Bennett, Marion Mafham, Xu Lin, Zhengming Chen, Jane Armitage, Robert Clarke
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness. <h3>Objective</h3> To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs. <h3>Data Sources</h3> PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018. <h3>Study Selection</h3> Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control. <h3>Data Extraction and Synthesis</h3> Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019. <h3>Main Outcomes and Measures</h3> Any fracture and hip fracture. <h3>Results</h3> In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97). <h3>Conclusions and Relevance</h3> In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.
Maternal antibiotic use during pregnancy and asthma in children: population-based cohort study and sibling design
Authors: Natalie C. Momen, Xiaoqin Liu
Journal: European Respiratory Journal (2021)

Antibiotic use during pregnancy may affect asthma risk in offspring. However, epidemiological studies yielded conflicting findings, with an observed association possibly confounded by shared familial factors. We sought to assess the association between maternal antibiotic use during pregnancy and childhood asthma in the offspring, by accounting for time-stable familial factors.We conducted a population-based cohort study and sibling study using data from Danish nationwide registers, which comprised 407 804 liveborn singletons from 2005 to 2011. Antibiotic use during pregnancy was defined as at least one antibiotic prescription filled by the mother from 1 month prior to pregnancy up until delivery, identified in the National Prescription Registry. First-time asthma in the offspring was determined by hospital treatment or asthma medication treatment after age 5 years. We estimated hazard ratios (HRs) of asthma using Cox regression in the population-based cohort and stratified Cox regression in the sibling cohort.Approximately 36.5% of pregnant women redeemed antibiotic prescriptions. Antibiotic use during pregnancy was associated with childhood asthma in cohort analyses (HR 1.21, 95% CI 1.18-1.24), but not in sibling analyses (HR 0.96, 95% CI 0.90-1.03). In the population-based analyses, higher risks of asthma were seen with longer duration of maternal antibiotic use, a higher number of prescriptions and prescriptions of multiple types of antibiotics. All these associations disappeared in the sibling analyses.The associations observed by previous studies for prenatal exposure to antibiotics and offspring asthma risk are likely to be due to confounding factors shared within families.