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Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human‐derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation‐related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs. [ABSTRACT FROM AUTHOR]

We investigated the effects of differential and nondifferential reinforcers on divided control by compound‐stimulus dimensions. Six pigeons responded in a delayed matching‐to‐sample procedure in which a blue or yellow sample stimulus flashed on/off at a fast or slow rate, and subjects reported its color or alternation frequency. The dimension to report was unsignaled (Phase 1) or signaled (Phase 2). Correct responses were reinforced with a probability of.70, and the probability of reinforcers for errors varied across conditions. Comparison choice depended on reinforcer ratios for correct and incorrect responding; as the frequency of error reinforcers according to a dimension increased, control (measured by log d) by that dimension decreased and control by the other dimension increased. Davison and Nevin's (1999) model described data when the dimension to report was unsignaled, whereas model fits were poorer when it was signaled, perhaps due to carryover between conditions. We are the first to test this quantitative model of divided control with reinforcers for errors and when the dimension to report is signaled; hence, further research is needed to establish the model's generality. We question whether divided stimulus control is dimensional and suggest it may instead reflect joint control by compound stimuli and reinforcer ratios. [ABSTRACT FROM AUTHOR]

Organisms may sometimes behave as if a contingency exists between behavior and consequences, even if this is not actually the case. Killeen (1978) suggested that such superstition occurs because of factors that bias subjects to behave "superstitiously" rather than because of failures of discrimination. We systematically replicated Killeen's experiment and compared contingency discrimination between different consequences. Six pigeons responded in a matching‐to‐sample procedure in which a response‐independent or response‐dependent stimulus change, food delivery, or blackout occurred. The pigeons reported whether the consequence was response dependent or response independent by choosing between two side keys. Discrimination was strongest after stimulus changes, weaker after blackouts, and weakest after food deliveries. These differences persisted even after additional training, suggesting asymmetries that may reflect differences in the disruptive effects of different consequences on remembering and/or behavioral mnemonics. Importantly, the pigeons were not biased to report response‐dependent consequences unless that response was consistent with locational biases; that is, they behaved "superstitiously" when there was a reason to be biased to do so. These findings corroborate Killeen's and demonstrate that behavior may deviate from contingencies not necessarily because subjects cannot discriminate those contingencies but because they are biased to behave otherwise. [ABSTRACT FROM AUTHOR]

Stimulus overselectivity describes strong control by one stimulus element at the expense of other equally relevant elements. Research suggests that control by underselected stimuli emerges following extinction of the overselected stimulus ("revaluation") and the emergence is larger when overselectivity is greater. We compared such revaluation effects with a control compound or condition in two experiments. Human participants chose between compound S+ and S‐ stimuli. Then, to assess control by compound‐stimulus elements, participants chose between individual elements in a testing phase without feedback. The S+ element chosen most often (the overselected element) underwent revaluation, during which choice of that element was extinguished and choice of a novel element reinforced. Thereafter, participants completed a retesting phase. Revaluation reduced choice of the overselected element. Choice of the underselected element decreased for participants with low overselectivity but increased for participants with high overselectivity. This was not the case for a control compound that did not undergo revaluation (Experiments 1 and 2) or in a control condition in which the overselected element continued to be reinforced during revaluation (Experiment 2). These findings suggest that overselectivity levels may modulate revaluation effects, and they also highlight the importance of the contingency change in postrevaluation changes in stimulus control. [ABSTRACT FROM AUTHOR]

The management of clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC) has progressed with the potential to avoid the morbidity of axillary lymph node dissection in patients with complete response to therapy. This study addresses the impact of pretreatment nodal burden and tumor subtype on axillary pathologic complete response (AXpCR) in patients treated with NAC to better inform axillary surgical management. A prospective database was reviewed to identify clinically node-positive patients who underwent NAC followed by axillary lymph node dissection. Patients were stratified in accordance with abnormal nodal burden on pretreatment axillary imaging defined as low (1-2 nodes) or high (≥3 nodes), and biologic subtype defined by hormone receptor (HR+, HR-) and HER2 (human epidermal growth factor receptor 2) status. The primary outcome was AXpCR. AXpCR was 43% in the study population. There was no difference in AXpCR between low and high nodal burden groups (44% versus 42%, P = 0.87). Subtype correlated to AXpCR (P < 0.001) with the highest rate (78%) in the HR−/HER2+ group. Overall, HER2+ patients had a significantly higher AXpCR than HER2- subtypes (66% versus 28% P < 0.001). HR and HER2 status were also predictive of AXpCR when comparing patient, tumor, and treatment variables. Biologic subtype better correlated with rates of AXpCR than nodal burden alone with the highest rates of AXpCR in HER2+ patients. Consideration of tumor biology is more informative than nodal burden when evaluating options for axillary management after NAC. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence suggests that the prevalence of eating disorders among Chinese women is a public health concern. Prior studies have drawn linkages between conflicting cultural values, identity confusion, and eating disorder symptomatology, which may be relevant for understanding the rise of eating disorders amidst China's rapid economic and sociocultural transformation. Here, we explore how women's experiences with traditional eating norms and modernizing norms of femininity may shape their food and body attitudes. Method: Chinese young adult women (N = 34; aged 18–22 years) participated in semi‐structured interviews focusing on experiences with norms surrounding eating and ideal feminine appearance, perceived conflict between these norms, and their responses to perceived conflict. Interviews were conducted via email (n = 27) or via Skype (n = 7). Participants were not asked about past or present diagnoses of eating disorders. Analysis of responses was guided by the principles of thematic analysis. Results: Women reported encounters with cultural eating norms and feminine appearance norms, and described factors that motivated continued or discontinued adherence to these norms. Women reported strategies of conflict resolution, which resulted in different emotional and behavioral outcomes including eating disorder symptoms. Discussion: Women's experiences with norms surrounding eating and appearance indicate the centrality of these encounters in the formation of individual and interpersonal values. Our findings suggest the importance for clinicians to assist clients in exploring the meanings behind internalized attitudes toward food and body, and to help clients balance interpersonal and individual needs. [ABSTRACT FROM AUTHOR]

Stimuli that provide information about likely future reinforcers tend to shift behavior, provided a reliable relation between the stimulus and the reinforcer can be discriminated. Stimuli that are apparently more reliable exert greater control over behavior. We asked how the subjective value (measured in terms of preference) of reinforcers associated with stimuli influences stimulus control. Five pigeons worked on a concurrent chains procedure in which half of all trials ended in a smaller reinforcer sooner, and the other half in a larger reinforcer later. In Signaled trials, the color and flash duration on the keys in the initial link signaled the outcome of the trial. In Conflicting probe trials, the color and the flash duration signaled conflicting information about the outcome of the trial. Choice in Signaled trials shifted toward the signaled outcome, but was never exclusive. In Conflicting probe trials, control was divided idiosyncratically between the 2 stimulus dimensions, but still favored the outcome with the higher subjective value. Thus, stimulus control depends not only on the perceived reliability of stimuli, but also on the subjective value of the outcome. [ABSTRACT FROM AUTHOR]

Previous research suggests that organisms allocate more attention to stimuli associated with higher reinforcer rates. This finding has been replicated several times when stimuli are trained together as compounds, but not in other procedures. Thus, the generality of the relation between relative reinforcer rates and divided attention is not well established. Therefore, we investigated whether relative reinforcer rates determine attention allocation when stimuli are trained separately and then encountered together. Pigeons learned to associate two colors and two frequencies of key light on/off alternation with a left or right comparison key in a symbolic 0-s delayed matching-to-sample task. Across conditions, we varied the probability of reinforcement associated with each stimulus dimension during training. After training, we introduced test trials in which a color and flash-frequency stimulus were presented simultaneously. During sample-stimulus presentation in test trials, all pigeons preferred the stimulus associated with the higher reinforcer rate, suggesting that more attention was allocated to that stimulus. Interestingly, such attention allocation did not result in preference for the comparison that matched that stimulus. Instead, all pigeons preferred the comparison that was physically closer to the stimulus associated with the higher reinforcer rate, suggesting that comparison choice was controlled by the location of that stimulus. Nevertheless, overall, our results provide the first evidence that relative reinforcer rates determine divided attention between separately trained stimuli and thus demonstrate the generality of the relation between relative reinforcement and attention allocation. We suggest several avenues for future research to establish further the generality of this relation. [ABSTRACT FROM AUTHOR]

Highlights • Control by stimuli signaling future reinforcer availability is often weaker in more certain environments. • We examined whether this was the case when reinforcer availability changed over time. • Across conditions, we varied the certainty of the next-reinforcer location at a particular time. • Stimuli strongly controlled behavior and environmental contingencies exerted weak control. • Control by stimuli and by the environment may depend on global, not local, environmental certainty. Abstract Several studies suggest that the degree of control by reinforcer ratios (environment tracking) and by exteroceptive stimuli that signal future reinforcer availability (signal following) depends on environmental certainty: As reinforcers become more likely at one location, environmental contingencies exert stronger control and exteroceptive stimuli exert weaker control. This research has not yet been extended to environments in which reinforcer availability changes across time, even though such changes are present in most natural environments. Thus, in the present experiment, we examined environment tracking and signal following in a concurrent schedule in which the reinforcer ratio reversed to its reciprocal 30 s after a reinforcer delivery and keylight-color stimuli signaled the likely or definite time or location of the next reinforcer. Across conditions, we manipulated environmental certainty by varying the probability of reinforcer deliveries on the locally richer key. This made the location of future reinforcers at a particular time more or less certain, but did not change the overall reinforcer ratio. Changes in local environmental certainty had little to no effect on environment tracking and signal following; in all conditions, keylight-color stimuli strongly controlled choice and reinforcer ratios exerted weak control. The present findings suggest that the extent of environment tracking and signal following is primarily determined by global, not local, environmental certainty. [ABSTRACT FROM AUTHOR]

Highlights • We studied stimulus generalization of response patterns in a multiple peak procedure. • Two training stimuli differentially signaled an FI 5-s and FI 20-s schedule. • Response-rate patterns to one training stimulus generalized nearly exclusively. • This research provides a strong starting point for future studies of generalization under FI schedules. • A thorough understanding of generalization under FI schedules requires analyzing a range of dependent variables. Abstract Stimulus generalization is typically assessed by analyzing overall response rates. Studies of generalization of response-rate patterns across time are less common, despite the ubiquitous nature of time and the strong temporal control over behavior in the natural world. Thus, we investigated generalization of response-rate patterns across time using a multiple peak procedure in pigeons. The frequency (fast or slow) at which the color of a keylight changed signaled a fixed-interval (FI) 5-s or 20-s schedule, counterbalanced across subjects. In peak trials, the frequency of keylight-color changes was varied. For the fast and slow training stimuli, response rates in peak trials were controlled by the arranged FI schedule value; they increased as the arranged reinforcer time approached, and decreased thereafter. Response-rate patterns to all test stimuli were similar to response-rate patterns to the slow training stimulus for all subjects. Thus, overall, strong generalization from the slow training stimulus to all test stimuli was evident, whereas there was little to no generalization from the fast training stimulus. These findings extend past research examining generalization of temporally controlled response-rate patterns, and provide a useful starting point for future investigations of generalization of fixed-interval responding. A thorough understanding of generalization processes requires analysis of dependent variables other than overall response rates, especially when responding is likely to be temporally controlled. [ABSTRACT FROM AUTHOR]

In concurrent schedules with a changeover delay (COD), choice often strongly favours the just-reinforced alternative immediately after a reinforcer delivery. These ‘preference pulses’ may be caused by a change in reinforcer availability created by the COD, and/or because the COD decreases the overall probability of switching. We investigated which explanation better accounts for preference pulses by arranging concurrent schedules that allowed us to separate the COD’s effects on reinforcer availability from its effects on the probability of switching. When the reinforcer ratio was 1:1, pulses were inconsistently accompanied by changes in reinforcer availability, but consistently accompanied by longer visits. These pulses appeared to be related only to the decreased probability of switching caused by the COD, providing the first evidence of pulses after reinforcers caused by the probability of switching alone. When the reinforcer ratio was 1:5 or 5:1; preference pulses were accompanied by changes in reinforcer availability and by longer visits. These pulses appeared to be related to the COD’s effects on reinforcer availability, although a small portion appeared to be related to low probability of switching. These findings suggest that the COD affects preference pulses by both decreasing the probability of switching and creating a change in reinforcer availability. [ABSTRACT FROM AUTHOR]

In concurrent schedules, reinforcers are often followed by a brief period of heightened preference for the just-productive alternative. Such 'preference pulses' may reflect local effects of reinforcers on choice. However, similar pulses may occur after nonreinforced responses, suggesting that pulses after reinforcers are partly unrelated to reinforcer effects. McLean, Grace, Pitts, and Hughes (2014) recommended subtracting preference pulses after responses from preference pulses after reinforcers, to construct residual pulses that represent only reinforcer effects. Thus, a reanalysis of existing choice data is necessary to determine whether changes in choice after reinforcers in previous experiments were actually related to reinforcers. In the present paper, we reanalyzed data from choice experiments in which reinforcers served different functions. We compared local choice, mean visit length, and visit-length distributions after reinforcers and after nonreinforced responses. Our reanalysis demonstrated the utility of McLean et al.'s preference-pulse correction for determining the effects of reinforcers on choice. However, visit analyses revealed that residual pulses may not accurately represent reinforcer effects, and reinforcer effects were clearer in visit analyses than in local-choice analyses. The best way to determine the effects of reinforcers on choice may be to conduct visit analyses in addition to local-choice analyses. [ABSTRACT FROM AUTHOR]

When short-term memory is assessed in the delayed matching-to-sample (DMTS) procedure, performance is better when cues signal larger reinforcer magnitudes or higher reinforcer probabilities for correct responding. Previous studies demonstrating signaled-magnitude or signaled-probability effects presented cues for a prolonged period during the sample stimulus and/or retention interval. The present study asked whether a signaled-probability effect would occur with brief post-sample cues that signaled the presence or absence of reinforcement. Five pigeons responded in a DMTS task in which sample stimuli were sometimes followed by a 0.5-s cue signaling that reinforcers would either be available or not available in the current trial, and the retention interval varied from 0.5 s to 20 s. A reliable signaled-probability effect was found when reinforcers were arranged independently and for all correct responses, whereas a smaller, less systematic effect was found when reinforcers were arranged dependently and probabilistically. These findings highlight the importance of reinforcement contingencies and contingency discriminability in remembering, and add to the evidence showing that cues signaling differential reinforcement in DMTS may affect processes during the retention interval and comparison phase, rather than attention to the sample stimulus. • We investigated how brief cues signaling the presence or absence of reinforcers affect memory performance. • Cues were presented for 0.5 s after the sample in a delayed matching-to-sample procedure. • In reinforced trials, reinforcers were arranged with p =.5 (Expt 1) or for all correct responses (Expt 2). • Accuracy was lower when cues signaled reinforcer absence in Expt 2. This effect was smaller and less systematic in Expt 1. • These findings highlight the role of discriminated reinforcement contingencies in remembering. [ABSTRACT FROM AUTHOR]

Summary Objectives This study examined long term swallowing outcomes of a cohort of head and neck cancer (HNC) patients identified at high risk of experiencing significant side effects from cancer treatment and were provided with a proactive PEG. Material and Methods Ninety-five HNC patients receiving definitive or adjuvant radiotherapy +/− chemotherapy were identified for proactive PEG placement using validated guidelines and followed for up to 3 years. Functional swallowing status was recorded at regular time points and data were collected on PEG use and duration in situ. Results Mean duration of enteral feeding was 125 days. PEGs remained in situ for approximately 7 months. PEG removal was achieved by 52% by 6 months and 86% by 1 year. Only 3 (3%) remained PEG dependent at 3 years. Over half (55%) had resumed a full non-texture modified diet by PEG removal. Conclusion Proactive PEG placement did not lead to high proportion of long term tube dependence in this high risk group and the majority achieved good swallowing outcomes. [ABSTRACT FROM AUTHOR]

The article focuses on male rape laws in countries such as Afghanistan, Great Britain and the U.S and the application of concepts of taboo in rape laws. Topics discussed include the history of male rape laws in these countries, the societal perception of rape in these countries along with its effect on the law, and the challenges faced by male rape victims in relation to their protection. It mentions the Prison Rape Elimination Act that dealt with sexual assault of prisoners.

We recently found that initial-link stimuli signaling trial outcomes (signals) in a concurrent-chains procedure exerted imperfect control during initial and terminal links. Here, we conducted a follow-up experiment to investigate further such imperfect control. Five pigeons worked on a concurrent-chains procedure in which one alternative led to a terminal link ending in a smaller-sooner reinforcer delivery, and the other in a larger-later reinforcer. During initial links of some trials, compound stimuli (signals) signaled the trial outcome. We assessed control by signal dimensions in Conflicting trials, in which the dimensions signaled conflicting outcomes. Unlike our previous experiment, signals remained present during terminal links. During initial links, preference favored the signaled key in Signaled trials, and the key signaled by the dimension exerting stronger control in Conflicting trials, suggesting strong signal control. Initial-link choice also depended on trial outcomes; preference was overall biased towards the smaller-sooner key. Terminal-link responding was primarily controlled by the key peck producing terminal-link entry, although some weak signal control was also evident. Thus, signal control during initial and terminal links was enhanced, and control by key-peck location during terminal links persisted, when signals remained present during terminal links. This suggests that our previous findings were partly related to temporal separation between signals and trial outcomes, and to history effects producing strong control by key-peck location. • We investigated how temporal separation between stimuli and outcomes affects stimulus control. • Pigeons responded for differentially signaled, delayed outcomes in a concurrent-chains procedure. • Behavior was controlled by the signals, and by key-peck location. • Signal control was stronger when the signals remained present until the outcome. • Interoceptive cues such as key-peck location may help bridge the gap between stimuli and future outcomes. [ABSTRACT FROM AUTHOR]

• Stimuli signaling reinforcement reduce responding on one alternative of a concurrent schedule. • We asked how signal reliability affects choice between signaled and unsignaled alternatives. • Signal reliability changed responding on the signaled alternative, but not the unsignaled alternative. • These results are consistent with matching theories, but not with research showing changes in responding on both alternatives. • Response competition and local reinforcer rates may modulate effects of signaled reinforcement in concurrent schedules. When reinforcer availability on one alternative of a concurrent schedule is signaled by a discriminative stimulus, responding on that alternative decreases. We investigated how the correlation between signal presentation and reinforcement (signal reliability) affects choice between signaled and unsignaled alternatives. Six pigeons responded in a concurrent schedule, in which reinforcers on one alternative were signaled by a key-color change. Across conditions, the probability of reinforcement following signal presentation varied (the probability in its absence was the complement). As signal reliability increased, response rates and latencies following signal onset on the signaled alternative decreased, whereas responding on the unsignaled alternative remained unchanged. Because the signal did not alter overall reinforcer rates, these findings are consistent with matching theories and research suggesting that responding on one alternative of a concurrent schedule depends on reinforcer, but not response, rates on other alternatives. However, these findings are inconsistent with others demonstrating concomitant changes in responding on signaled and unsignaled alternatives. We consider whether a response-competition account of concurrent performance can explain these discrepancies, and suggest avenues for future studies to investigate the mechanisms underlying effects of signaled reinforcement in concurrent schedules. [ABSTRACT FROM AUTHOR]

Prenatal diagnosis of congenital heart disease (CHD) often leads to anxiety, depression, and traumatic stress in expectant mothers, with long-term implications for the child and family. However, psychosocial intervention is rarely incorporated into prenatal care. HEARTPrep is a virtually delivered psychosocial intervention aimed at reducing distress and social isolation and increasing parenting self-efficacy and hope for mothers expecting a baby with CHD to promote long-term child/family well-being. This study evaluated the feasibility and acceptability of HEARTPrep. Participants were mothers receiving cardiology care for a fetal CHD diagnosis. Partners could participate with the mother. HEARTPrep was delivered through a mobile app and telehealth. Feasibility was assessed through enrollment/retention rates. Acceptability was assessed through 20 Likert-scale and five open-ended questions. Of 39 recruited mothers, 35 (90%) enrolled. Half of partners (48%) also participated. Twenty-seven of 35 enrolled mothers (77%) completed HEARTPrep. On a scale from 0 (Not at All) to 4 (Very), mean item acceptability scores ranged from 3.5 to 3.9. Mothers reported HEARTPrep helped them feel less distressed (mean: 3.74), less alone (3.84), more prepared (3.89), and more hopeful (3.84). Opportunities to process emotions, develop coping skills, learn with their partner, navigate relationships, understand they are not alone, connect with peer support, access resources, and prepare for stressors were described as helpful. HEARTPrep is feasible and acceptable for mothers expecting a baby with CHD. Future research will evaluate its efficacy in preventing/reducing maternal mental health problems and improving postnatal clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Blunt trauma patients with potential cervical spine injury are traditionally immobilised in rigid collars. Recently, this has been challenged. The present study's objective was comparison of the rate of patient‐oriented adverse events in stable, alert, low‐risk patients with potential cervical spine injuries immobilised in rigid versus soft collars. Methods: Unblinded, prospective quasi‐randomised clinical trial of neurologically intact, adult, blunt trauma patients assessed as having potential cervical spine injury. Patients were randomised to collar type. All other aspects of care were unchanged. Primary outcome was patient‐reported discomfort related to neck immobilisation by collar type. Secondary outcomes included adverse neurological events, agitation and clinically important cervical spine injuries (clinical trial registration number: ACTRN12621000286842). Results: A total of 137 patients were enrolled: 59 patients allocated to a rigid collar and 78 to a soft collar. Most injuries were from a fall <1 m (54%) or a motor vehicle crash (21.9%). Median neck pain score of collar immobilisation was lower in the soft collar group (3.0 [interquartile range 0–6.1] vs 6.0 [interquartile range 3–8.8], P < 0.001). The proportion of patients with clinician‐identified agitation was lower in the soft collar group (5% vs 17%, P = 0.04). There were four clinically important cervical spine injuries (two in each group). All were treated conservatively. There were no adverse neurological events. Conclusions: Use of soft rather than rigid collar immobilisation for low‐risk blunt trauma patients with potential cervical spine injury is significantly less painful for patients and results in less agitation. A larger study is needed to determine the safety of this approach or whether collars are required at all. [ABSTRACT FROM AUTHOR]

This study aims to identify independent factors associated with cervical spinal injuries in head-injured patients. The extent of injuries to other body parts was assessed by the Abbreviated Injury Scale (AIS) and was included in the analysis. Consecutive head-injured patients admitted via the emergency department from January 1, 2014 to December 31, 2016 were retrospectively reviewed. The inclusion criteria were head-injured patients with an Abbreviated Injury Scale (AIS) score ≥2 (i.e., head injuries with intracranial hematoma or skull fracture). Patients with minor head injuries with only scalp abrasions or superficial lacerations without significant intracranial injuries (i.e., head injury AIS score = 1) were excluded. The primary outcome was to identify independent predictors associated with cervical spinal injuries in these head-injured patients. Univariate and multivariable analyses were conducted. A total of 1105 patients were identified. Of these patients, 11.2% (n = 124) had cervical spinal injuries. Univariate and multivariable analyses identified male gender (P = 0.006), the presence of thoracic injury (including rib fracture, hemothorax, or pneumothorax) (P = 0.010), and hypotension with systolic blood pressure <90 mm Hg on admission (P = 0.009) as independent predictors for cervical spinal injury in head-injured patients. This study showed that about 1 in 10 patients with significant head injury had cervical spine injury, usually associated with fracture or dislocation. Male gender, the presence of thoracic injury, and hypotension on admission were independent risk factors associated with cervical spinal injuries. [ABSTRACT FROM AUTHOR]

Metformin, an anti-hyperglycemic drug, has been known to have antitumor properties for around 15 years. Although there are a number of reports attributing the antitumor function of metformin to its impact on energy homeostasis and oxygen re-distribution in tumor microenvironment, detailed mechanisms remain largely unknown. In the past several years, there is an increasing number of publications indicating that metformin can affect various immunological components including lymphocytes, macrophages, cytokines and several key immunological molecules in both human and animal studies. These interesting results appear to be in line with emerging data that suggest associations between immune responses and energy homeostasis/oxygen re-distribution, which may explain effective impacts of metformin on immunotherapies against autoimmune diseases as well as cancers. This review article is to analyse and discuss recent development in the above areas with aim to justify metformin as a new adjuvant for immunotherapy against human cancers. We hope that our summary will help to optimize the application of metformin for various types of human cancers. [ABSTRACT FROM AUTHOR]

Chronic subdural haematoma (CSDH) is a common neurosurgical condition. Burr-hole for drainage is an effective treatment. However, recurrence can be up to 8–33% and is associated with morbidities and mortalities. The underlying pathogenesis was postulated to be localised inflammation and pathological aberrant vessels formation. Atorvastatin, an HMG-CoA reductase inhibitor, is a type of lipid-lowering medication. In animal studies and a preliminary clinical trial, Atorvastatin was shown to be effective in the treatment of CSDH. It was found to inhibit inflammation and promote vascular maturation at the neomembrane of CSDH. Our study aimed to investigate the efficacy of Atorvastatin in CSDH. During the study period from January to December 2014, Atorvastatin was used in 12 CSDH patients with Glasgow Coma Scale (GCS) 13–15 or Markwalder’s Grading Scale (MGS) Grade 0–2. They were retrospectively compared with GCS- and MGS-matched controls who had not used statin. Improvement with haematoma resolution at 3 months was 75% (9/12) for the Atorvastatin group, versus 42% (5/12) for the Control group (p = 0.0977). The risk of deterioration requiring burr-hole drainage was 16.7% (2/12) in the Atorvastatin group, versus 58.3% (7/12) in the Control group (p = 0.0447). The Odds Ratio (OR) of deterioration requiring burr-hole drainage with Atorvastatin was 0.143 (95%CI: 0.021–0.958), which favours the use of Atorvastatin in CSDH (p = 0.0451). The Number needed to treat (NNT) was 2.4 (p = 0.0447; 95%CI: 1.31–14.93). In conclusion, this retrospective cohort comparison study has shown that CSDH with Atorvastatin had a lower rate of deterioration and burr-hole drainage. [ABSTRACT FROM PUBLISHER]

From the foods we eat and the houses we construct, to our religious practices and political organization, to who we can marry and the types of games we teach our children, the diversity of cultural practices in the world is astounding. Yet, our ability to visualize and understand this diversity is limited by the ways it has been documented and shared: on a culture-by-culture basis, in locally-told stories or difficult-to-access repositories. In this paper we introduce D-PLACE, the Database of Places, Language, Culture, and Environment. This expandable and open-access database (accessible at ) brings together a dispersed corpus of information on the geography, language, culture, and environment of over 1400 human societies. We aim to enable researchers to investigate the extent to which patterns in cultural diversity are shaped by different forces, including shared history, demographics, migration/diffusion, cultural innovations, and environmental and ecological conditions. We detail how D-PLACE helps to overcome four common barriers to understanding these forces: i) location of relevant cultural data, (ii) linking data from distinct sources using diverse ethnonyms, (iii) variable time and place foci for data, and (iv) spatial and historical dependencies among cultural groups that present challenges for analysis. D-PLACE facilitates the visualisation of relationships among cultural groups and between people and their environments, with results downloadable as tables, on a map, or on a linguistic tree. We also describe how D-PLACE can be used for exploratory, predictive, and evolutionary analyses of cultural diversity by a range of users, from members of the worldwide public interested in contrasting their own cultural practices with those of other societies, to researchers using large-scale computational phylogenetic analyses to study cultural evolution. In summary, we hope that D-PLACE will enable new lines of investigation into the major drivers of cultural change and global patterns of cultural diversity. [ABSTRACT FROM AUTHOR]

Scholars have debated naturalistic theories of religion for thousands of years, but only recently have scientists begun to test predictions empirically. Existing databases contain few variables on religion, and are subject to Galton’s Problem because they do not sufficiently account for the non-independence of cultures or systematically differentiate the traditional states of cultures from their contemporary states. Here we present Pulotu: the first quantitative cross-cultural database purpose-built to test evolutionary hypotheses of supernatural beliefs and practices. The Pulotu database documents the remarkable diversity of the Austronesian family of cultures, which originated in Taiwan, spread west to Madagascar and east to Easter Island–a region covering over half the world’s longitude. The focus of Austronesian beliefs range from localised ancestral spirits to powerful creator gods. A wide range of practices also exist, such as headhunting, elaborate tattooing, and the construction of impressive monuments. Pulotu is freely available, currently contains 116 cultures, and has 80 variables describing supernatural beliefs and practices, as well as social and physical environments. One major advantage of Pulotu is that it has separate sections on the traditional states of cultures, the post-contact history of cultures, and the contemporary states of cultures. A second major advantage is that cultures are linked to a language-based family tree, enabling the use phylogenetic methods, which can be used to address Galton’s Problem by accounting for common ancestry, to infer deep prehistory, and to model patterns of trait evolution over time. We illustrate the power of phylogenetic methods by performing an ancestral state reconstruction on the Pulotu variable “headhunting", finding evidence that headhunting was practiced in proto-Austronesian culture. Quantitative cross-cultural databases explicitly linking cultures to a phylogeny have the potential to revolutionise the field of comparative religious studies in the same way that genetic databases have revolutionised the field of evolutionary biology. [ABSTRACT FROM AUTHOR]

The discovery of a new series of selective S1P 1 agonists is described. This series of piperazinyl-oxadiazole derivatives was rapidly optimized starting from high-throughput screening hit 1 to afford potent and selective lead compound 10d . Further SAR studies showed that 10d was converted to the active phosphate metabolite 29 in vivo. Oral administration of compound 10d to rats was shown to induce lymphopenia at 3 mg/kg. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two common betacoronaviruses, which are still causing transmission among the human population worldwide. The major difference between the two coronaviruses is that MERS-CoV is now causing sporadic transmission worldwide, whereas SARS-CoV-2 is causing a pandemic outbreak globally. Currently, different guidelines and reports have highlighted several diagnostic methods and approaches which could be used to screen and confirm MERS-CoV and SARS-CoV-2 infections. These methods include clinical evaluation, laboratory diagnosis (nucleic acid-based test, protein-based test, or viral culture), and radiological diagnosis. With the presence of these different diagnostic approaches, it could cause a dilemma to the clinicians and diagnostic laboratories in selecting the best diagnostic strategies to confirm MERS-CoV and SARS-CoV-2 infections. Therefore, this review aims to provide an up-to-date comparison of the advantages and limitations of different diagnostic approaches in detecting MERS-CoV and SARS-CoV-2 infections. This review could provide insights for clinicians and scientists in detecting MERS-CoV and SARS-CoV-2 infections to help combat the transmission of these coronaviruses. [ABSTRACT FROM AUTHOR]

(2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes. [ABSTRACT FROM AUTHOR]

Background: Different mechanical supporting strategies to the joints in the upper extremity (UE) may lead to varied rehabilitative effects after stroke. This study compared the rehabilitation effectiveness achieved by electromyography (EMG)-driven neuromuscular electrical stimulation (NMES)-robotic systems when supporting to the distal fingers and to the proximal (wrist-elbow) joints.Methods: Thirty subjects with chronic stroke were randomly assigned to receive motor trainings with NMES-robotic support to the finger joints (hand group, n = 15) and with support to the wrist-elbow joints (sleeve group, n = 15). The training effects were evaluated by the clinical scores of Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Modified Ashworth Scale (MAS) before and after the trainings, as well as 3 months later. The cross-session EMG monitoring of EMG activation level and co-contraction index (CI) were also applied to investigate the recovery progress of muscle activations and muscle coordination patterns through the training sessions.Results: Significant improvements (P < 0.05) in FMA full score, FMA shoulder/elbow (FMA-SE) and ARAT scores were found in both groups, whereas significant improvements (P < 0.05) in FMA wrist/hand (FMA-WH) and MAS scores were only observed in the hand group. Significant decrease of EMG activation levels (P < 0.05) of UE flexors was observed in both groups. Significant decrease in CI values (P < 0.05) was observed in both groups in the muscle pairs of biceps brachii and triceps brachii (BIC&TRI) and the wrist-finger flexors (flexor carpi radialis-flexor digitorum) and TRI (FCR-FD&TRI). The EMG activation levels and CIs of the hand group exhibited faster reductions across the training sessions than the sleeve group (P < 0.05).Conclusions: Robotic supports to either the distal fingers or the proximal elbow-wrist could achieve motor improvements in UE. The robotic support directly to the distal fingers was more effective than to the proximal parts in improving finger motor functions and in releasing muscle spasticity in the whole UE.Clinical Trial Registration: ClinicalTrials.gov , identifier NCT02117089; date of registration: April 10, 2014. https://clinicaltrials.gov/ct2/show/NCT02117089. [ABSTRACT FROM AUTHOR]