bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal Clinically Important Difference in AIMS Score Based on CGIC and PGIC in Patients With Tardive Dyskinesia Treated With Deutetrabenazine
Authors: Barkay Hadas , Hauser Robert A. , Wilhelm Amanda , Wieman Maria , Gordon Mark Forrest , Savola Juha-Matti 
Published: May 2021

AbstractBackgroundDeutetrabenazine is FDA approved for tardive dyskinesia (TD) based on two 12-week, placebo-controlled studies evaluating safety and efficacy in patients with baseline Abnormal Involuntary Movement Scale (AIMS) score ≥6. Deutetrabenazine reduced overall AIMS scores compared with placebo in ARM-TD (–3.0 vs –1.6, P=0.019) and AIM-TD (24 mg/day, –3.2 vs –1.4, P=0.003; 36 mg/day, –3.3 vs –1.4, P=0.001). This analysis assessed Minimal Clinically Important Difference (MCID) in AIMS score in patients with TD treated with deutetrabenazine.MethodsMCID is the smallest change from baseline in AIMS score that is meaningful for patients. MCID analyses were performed based on Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors described by Hauser et al., where MCID is the difference between patients treated with deutetrabenazine who were minimally improved and patients treated with placebo who were unchanged. Additional MCID definitions were explored: difference between patients who demonstrated treatment improvement versus those who did not (Method 2); difference between patients who demonstrated treatment success versus those who did not (Method 3).Results295 patients were analyzed. Based on PGIC, the suggested MCID was –2.8. Results were similar for Method 2 (75% of patients had treatment improvement; MCID = –2.8) and Method 3 (38% of patients had treatment success; MCID = –2.6). Based on CGIC, the suggested MCID was –2.6. Results were similar for Method 2 (76% of patients had treatment improvement; MCID = –2.8) and Method 3 (41% of patients had treatment success; MCID = –3.0). Therefore, the suggested MCID for deutetrabenazine is –3.ConclusionsThe MCID for change in AIMS score based on PGIC and CGIC for deutetrabenazine was –3 regardless of the analytical method. Findings suggest an AIMS score reduction of ~3 is associated with clinically meaningful improvement in TD symptoms.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Comparative Bioavailability of Amphetamine Extended-Release Oral Suspension and Extended-Release Mixed Amphetamine Salts
Authors: Pardo Antonio , Bouhajib Mohammed , Rafla Eman , King Thomas R. , Kando Judith C. 
Published: May 2021

AbstractPurposeThis open-label, single-dose, randomized, two-period, two-treatment, two-sequence, crossover study evaluated the comparative bioavailability between amphetamine extended-release oral suspension (treatment A: AMPH EROS, Dyanavel XR 2.5 mg/mL, 18.8 mg amphetamine base per 7.5 mL) and extended-release mixed amphetamine salts (treatment B: ER MAS, Adderall XR 30 mg capsules, equivalent to 18.8 mg amphetamine base per capsule) after a single dose in healthy adult subjects, under fasted conditions.MethodsThe crossover design allowed for intra-subject PK comparisons. Relative comparable bioavailability was determined by a statistical comparison of the AUC and Cmax parameters for both d- and l-amphetamine, where the geometric mean ratios for AUC and Cmax were within the 90% confidence limits (80.0%–125.0%) to determine comparable bioavailability between test products. Subjects in sequence 1 received treatment A followed by B; subjects in sequence 2 received treatment B followed by treatment A. PK samples were obtained at 0 (pre-dose) through 60 hours post-dose. The safety assessment was based on reported frequency and severity of adverse events.ResultsThirty (30) subjects were enrolled and 28 completed. The mean age of subjects was 35 years, with a mean BMI of 25.9 kg/m2. Most subjects were Male (63.3%) and Black (56.7%). The geometric mean ratios for Cmax and all AUC measurements were within the 80–125% bound indicating comparable bioavailability between both test products. Both test products were generally well-tolerated with no serious AEs reported.ConclusionsThe bioavailability of a single 7.5 mL dose of AMPH EROS 2.5 mg/mL was comparable to a single 30 mg capsule dose of ER MAS. AMPH EROS (both d- and l-amphetamine) showed equivalent peak and overall exposure to ER MAS under fasted conditions.FundingTris Pharma, Inc.
The Effectiveness of De-Escalation Techniques as Compared to Physical Restraint/Seclusion on Inpatient Psychiatric Units: A Quantitative Systematic Review
Authors: Chase Shavar 
Published: May 2021

AbstractBackgroundRestraint and seclusion were considered a form of treatment but consistently has led to physical and mental injuries to staff and patients. De-escalation has been viewed as a safer option. Understanding which intervention yields decreased injuries, aggression and violence will guide policy and inform practice.ObjectivesTo identify which intervention leads to decreased physical and psychological injury to patients and staff.MethodsThe frequency of physical injuries to patients and staff from aggressive patients; frequency of psychological injuries to patients and staff from violent, aggressive incidents; frequency of violence, agitation and aggression; competence of staff at managing aggression and violence were evaluated.ResultsFourteen studies were included in this review. There are many forms of de-escalation. Studies where techniques were taught to staff, the intervention was effective in decreasing injury in approximately half the studies. De-escalation techniques taught to patients decreased injury in 100% of the studies included in this review.ConclusionConsensus on which intervention works best could not be reached, nor is there overwhelming evidence for a particular type of de-escalation better suited for decreasing aggression and violence. Caution should be exercised when choosing a de-escalation technique for implementation in institutions due to lack of regulating agencies that inform practice and standards. In addition, the literature lacks best practices for de-escalation techniques backed by evidence. Restraint and seclusion should be used as a last resort due to inherent risk associated with the intervention.
Methylphenidate-Induced Chorea Due to Possible Cytochrome P450 Metabolism Heterogeneity - A Rare Case
Authors: Jadapalle Sree Latha Krishna , McCray Edwin , Masoud John Azat , Kortz Michael W. 
Published: May 2021

AbstractBackgroundChorea is defined as a hyperactive movement disorder associated with involuntary, quick, and unpredictable muscle contractions of the limbs, face, and trunk. The unpredictable nature of these movements includes variation in speed, timing, and direction of movement. A wide variety of medications, medical conditions and illicit drugs have been associated with movement disorders. Examples include a multitude of antipsychotic induced movement disorders and dyskinesia related to dopaminergic agents, like levodopa and metoclopramide. Dyskinesias have been associated with psycho-stimulant use, such as methylphenidate. However, most cases reported were associated with large doses or chronic use. Aside from dyskinesia, methylphenidate is known to be associated with tic disorder, tremor, and muscle spasm. However, this case reported is unlike any of the above described and involved the development of chorea after only 2 days of moderate doses of methylphenidate, in a patient on chronic methadone maintenance treatment, with successful arrest of symptoms following discontinuation of the methylphenidate.Case PresentationA 47-year-old female was admitted to our hospital after presenting to the emergency department with 1 week of violent flailing movements. The ballistic flailing movements started acutely after 2 days of initiating methylphenidate in addition to her chronic methadone treatment and 2-week period of initiation of paroxetine. Lab work showed normal CBC, CMP, CRP, CK, and TSH. Urine drug screen, CT angiography of the head, and Huntington’s disease testing were all unremarkable, suggesting a decreased likelihood of illicit drugs, traumatic brain injury, or Huntington’s disease etiologies. Confirmation of the diagnosis was made as the chorea symptoms abruptly resolved upon discontinuation of methylphenidate and administration of intravenous Benadryl. The patient has been on methadone alone for 11 months and methylphenidate alone 2 years back with no involuntary movements or any similar presentation that shows the possibility of drug interaction through cytochrome P450 metabolism between Methylphenidate and methadone.ConclusionWe are presenting a rare case report that adds on to the scarce literature on methylphenidate-induced chorea. It also challenges the consulting psychiatrists to broaden their differential diagnosis for acute onset of choreiform movement disorders. This unique case intrigues the thought process to consider the interaction of methylphenidate in the presence of cytochrome P450 2D6 and 3A4 inhibitors like methadone.
The barriers, benefits and training needs of clinicians delivering psychological therapy via video
Authors: Buckman Joshua E. J. , Saunders Rob , Leibowitz Judy , Minton Rebecca 
Published: May 2021

Abstract

Background:
Due to the COVID-19 pandemic, mental health services have had to offer psychological therapy via video with little time to prepare or mitigate potential problems. Identifying the barriers, benefits and training needs highlighted by clinicians may support the effective delivery of care.

Method:
Changes in the mode therapy sessions were delivered in during 2020 were assessed in two high-volume psychological therapies services. Sixty-six therapists completed a survey about their experiences of delivering therapy via video.

Results:
The lockdown in March 2020 precipitated a dramatic shift from face-to-face to telephone and video-delivered sessions. Most clinicians (89%) found video-based sessions acceptable. Barriers to effective delivery included technological issues, problems with online platforms, and feeling more tired after sessions. Benefits included generalised learning from behavioural work, improvements in efficiency and in the therapeutic relationship, particularly in comparison with telephone-based sessions. Tutorials and support guides were recommended to maximise use of sessions via video.

Conclusions:
Video-delivered therapy was liked by clinicians and preferred to telephone-based sessions. Issues with platforms, internet connections and access for patients need addressing, local troubleshooting guides, video-based tutorials and greater support for low-intensity therapists to maximise uptake of video sessions where appropriate, may be beneficial.
Skewness in the literature on infectious livestock diseases in an emerging economy – the case of Vietnam
Authors: Rajala Elisabeth , Lee Hu Suk , Nam Nguyen Hoai , Huong Chu Thị Thanh , Son Hoang Minh , Wieland Barbara , Magnusson Ulf 
Published: May 2021

AbstractLivestock production has increased in many emerging economies, but productivity is often substantially impaired by infectious diseases. The first step towards improved livestock health and productivity is to map the presence of livestock diseases. The objective of this review was to summarize studies conducted on such diseases in an emerging economy, Vietnam, and thereby identifying knowledge gaps that may inform the design of surveillance and control programs. Few studies were found to evaluate the distribution of infectious livestock diseases other than avian influenza. Also, many regions with dense livestock populations had received little attention in terms of disease investigation. A large proportion of the studies dealt with zoonoses and food-borne infections which might be due to funding agencies priorities. On the contrary, studies targeting infections that affect livestock and their productivity were few. We think that this limitation in scientific reports on infectious diseases that only affect livestock productivity is a common phenomenon in low and lower middle income countries. More science-based data on such diseases would help policymakers to prioritize which livestock diseases should be subject to animal health programs aimed to support rural livelihoods and economic development.
Dynamics of a Solidifying Icy Satellite Shell
Authors: Buffo J. J. , Meyer C. R. , Parkinson J. R. G. 
Published: May 2021

AbstractOcean worlds have been identified as high‐priority astrobiology targets due to the link between life and liquid water. Young surface terrain on many icy bodies indicates that they support active geophysical cycles that may facilitate ocean‐surface transport that could provide observables for upcoming missions. Accurately interpreting spacecraft observations requires constraining the relationship between ice shell characteristics and interior dynamics. On Earth, the composition, physical characteristics, and bioburden of ocean‐derived ices are related to their formation history and parent fluid composition. In such systems, the ice–ocean interface, which exists as a multiphase mushy layer, dictates the overlying ice’s properties and evolution. Inclusion of the physics governing these boundaries is a novel strategy in modeling planetary ices and thus far has been limited to 1D approaches. Here, we present results from 2D simulations of an archetypal ice–ocean world. We track the evolution of temperature, salinity, porosity, and brine velocity within a thickening ice shell enabling us to place improved constraints on ice–ocean world properties, including the composition of planetary ice shells, the thickness and hydraulic connectivity of ice–ocean interfaces, and heterogeneous dynamics/structures in the interfacial mushy layer. We show that stable eutectic horizons are likely a common feature of ice–ocean worlds and that ocean composition plays an important role in governing the structure and dynamics of the interface, including the formation of chemical gradient‐rich regions within the mushy layer. We discuss the geophysical and astrobiological implications of our results and highlight how they can be validated by instrument‐specific measurements.
Lake Outflow and Hillslope Lateral Inflows Dictate Thermal Regimes of Forested Streams Draining Small Lakes
Authors: Leach Jason A. , Neilson Bethany T. , Buahin Caleb A. , Moore R. Dan , Laudon Hjalmar 
Published: May 2021

AbstractEmpirical studies have highlighted the important influence of lakes on stream temperature at landscape scales, even when lakes comprise just a small fraction of the catchment area. However, only a few studies have focused on the hydrologic and thermal processes underpinning these landscape patterns. We collected detailed field measurements at a boreal stream that drains a headwater lake and used these data within a process‐based stream temperature model to, (a) document the downstream extent of lake influences at both seasonal and event‐based timescales, (b) assess the hydrologic and thermal processes that control the observed downstream variability, and (c) compare downstream temperature for streams with and without a headwater lake. Summer and autumn lake outlet temperatures were elevated compared to hillslope lateral inflow temperatures. During periods of low lake outflow, stream temperatures decreased rapidly downstream as local energy fluxes, primarily lateral inflows from the hillslopes and hyporheic exchange, overwhelmed the lake effects. The lake influence on downstream temperature was the greatest during periods of high lake outflow and persisted at least 1.4 km downstream. Since lakes can moderate and delay upstream rainfall runoff response, periods of high lake outflow and high hillslope inflow rates were generally out‐of‐phase. This difference in timing of warm lake outlet and cool hillslope water creates a dynamic thermal environment downstream of the small lake. Such lakes are ubiquitous in northern landscapes, and accounting for the competing influence of lake and hillslope contributions on downstream water temperature is critical for predicting how network‐scale thermal regimes will respond to environmental change.
Two Distinct Modes of Tropical Convection Structure and Associated Climate Variability Over East Asia/Korea in January
Authors: Yeo Sae‐Rim , Kim WonMoo , Kim Baek‐Min 
Published: May 2021

AbstractTwo distinct modes of convection variability over the tropical Indo‐Pacific during January and the associated climate variability over East Asia, especially in Korea, are identified. The first mode (empirical orthogonal functions [EOF1]) exhibits a zonal dipole structure of suppressed convection over the Maritime Continent and enhanced convection over the tropical central Pacific, which represents a typical El Niño response. The second mode (EOF2) is a tripole pattern showing suppressed convection over the eastern Indian Ocean and east of the dateline, and enhanced convection over the tropical western Pacific. The temporal variation of EOF2 exhibits a distinctive positive trend and stronger amplitude after the early 2000s. During the positive phase of EOF2, the sea surface temperature (SST) anomaly pattern displays central Pacific (CP) El Niño, and the associated atmospheric circulation pattern is characterized by a high‐pressure anomaly that directly affects Korea and induces warm and dry conditions. Of the winter months, these distinctive features of EOF2 are particularly evident in January. This study attempts to identify a possible mechanism for the relatively unfamiliar convection structure of EOF2. Enhanced Madden‐Julian Oscillation (MJO) activity over the tropical western Pacific, namely, phases 5, 6, and 7, plays a crucial role in driving the positive phase of the EOF2 convection structure. The recent CP type El Niño, which does not accompany the cold SST anomaly and suppressed convection over the Maritime Continent, may provide favorable conditions for the frequent occurrence of MJO phases 5, 6, and 7.
Serotonin transporter availability increases in patients recovering from a depressive episode
Authors: Svensson Jonas E. , Svanborg Cecilia , Plavén-Sigray Pontus , Kaldo Viktor , Halldin Christer , Schain Martin , Lundberg Johan 
Published: May 2021

AbstractMolecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using [11C]MADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p < 0.001). [11C]MADAM binding in patients increased in the composite region after treatment (p = 0.01), while no change was observed in the median raphe (p = 0.51). No significant difference between patients at baseline and healthy controls were observed in the composite region (p = 0.97) or the median raphe (p = 0.95). Our main finding was that patients suffering from a depressive episode show an overall increase in cerebral serotonin transporter availability as symptoms are alleviated. Our results suggest that previously reported cross-sectional molecular imaging findings of the serotonin transporter in depression most likely reflect the depressive state, rather than a permanent trait. The finding adds new information on the pathophysiology of major depressive disorder.
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome
Authors: Wang Yucai , Sinha Sutapa , Wellik Linda E. , Secreto Charla R. , Rech Karen L. , Call Timothy G. , Parikh Sameer A. , Kenderian Saad S. , Muchtar Eli , Hayman Suzanne R. , Koehler Amber B. , Van Dyke Daniel L. , Leis Jose F. , Slager Susan L. , Dong Haidong , Kay Neil E. , He Rong , Ding Wei 
Published: May 2021

AbstractRichter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such asTP53andNOTCH1mutations. However, it is unclear what immune microenvironment changes are associated with RS. In this study, we analyzed expression of immune checkpoint molecules and infiltration of immune cells in nodal samples, and peripheral blood T-cell diversity in 33 CLL and 37 RS patients. Compared to CLL, RS nodal tissue had higher PD-L1 expression in histiocytes and dendritic cells (median 16.6% vs. 2.8%,P < 0.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%,P < 0.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%,P < 0.01) and CD163-positive macrophages (median 23.4% vs. 9.1%,P < 0.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median [25th–75th], 0.107 [0.070–0.209] vs. 0.233 [0.111–0.406],P = 0.046), suggesting that T cells in RS patients were significantly more diverse than in CLL patients. Collectively these data suggest that CLL and RS have distinct immune signatures. Better understanding of the immune microenvironment is essential to improve immunotherapy efficacy in CLL and RS.
3D mechanical characterization of single cells and small organisms using acoustic manipulation and force microscopy
Authors: Läubli Nino F. , Burri Jan T. , Marquard Julian , Vogler Hannes , Mosca Gabriella , Vertti-Quintero Nadia , Shamsudhin Naveen , deMello Andrew , Grossniklaus Ueli , Ahmed Daniel , Nelson Bradley J. 
Published: May 2021

AbstractQuantitative micromechanical characterization of single cells and multicellular tissues or organisms is of fundamental importance to the study of cellular growth, morphogenesis, and cell-cell interactions. However, due to limited manipulation capabilities at the microscale, systems used for mechanical characterizations struggle to provide complete three-dimensional coverage of individual specimens. Here, we combine an acoustically driven manipulation device with a micro-force sensor to freely rotate biological samples and quantify mechanical properties at multiple regions of interest within a specimen. The versatility of this tool is demonstrated through the analysis of single Lilium longiflorum pollen grains, in combination with numerical simulations, and individual Caenorhabditis elegans nematodes. It reveals local variations in apparent stiffness for single specimens, providing previously inaccessible information and datasets on mechanical properties that serve as the basis for biophysical modelling and allow deeper insights into the biomechanics of these living systems.