Effects of Voice Pitch on Social Perceptions Vary With Relational Mobility and Homicide Rate.

Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men's perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women's perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates.

Chemoselective Post-Synthesis Modification of Pyridyl-Substituted, Aromatic Phosphorus Heterocycles: Cationic Ligands for Coordination Chemistry.

Triazaphospholes are potential polydentate ligands due to the presence of both phosphorus and nitrogen donor atoms within the aromatic 5-membered heterocycle. The incorporation of an additional pyridyl-substituent opens up the possibility of a post-synthesis modification via chemoselective and also stepwise alkylation exclusively of the nitrogen atoms. This can be controlled by the choice and by the stoichiometry of the electrophile and allows the targeted synthesis of a variety of novel mono- and dicationic ligands. Reaction with Cu(I)-halides causes the formation of cuprates of the type [CuXn](n-1)-, which enables coordination of the π-acidic phosphorus donor to the negatively charged metal core, which is favored over the coordination by a strongly σ-donating nitrogen atom. The use of cationic triazaphosphole derivatives can be used as a strategy to enforce the coordination of the ligand to an electron rich metal solely via the phosphorus atom. However, there is a subtle balance between the formation of either coordination polymers or dimeric structures, as the substitution pattern on the heterocycle and the nature of the halide have a large influence on the coordination motifs formed.

Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis.

BACKGROUND: Bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are amongst the bone-modifying agents used as supportive treatment in women with breast cancer who do not have bone metastases. These agents aim to reduce bone loss and the risk of fractures. Bisphosphonates have demonstrated survival benefits, particularly in postmenopausal women. OBJECTIVES: To assess and compare the effects of different bone-modifying agents as supportive treatment to reduce bone mineral density loss and osteoporotic fractures in women with breast cancer without bone metastases and generate a ranking of treatment options using network meta-analyses (NMAs). SEARCH METHODS: We identified studies by electronically searching CENTRAL, MEDLINE and Embase until January 2023. We searched various trial registries and screened abstracts of conference proceedings and reference lists of identified trials. SELECTION CRITERIA: We included randomised controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for women with breast cancer without bone metastases. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of included studies and certainty of evidence using GRADE. Outcomes were bone mineral density, quality of life, overall fractures, overall survival and adverse events. We conducted NMAs and generated treatment rankings. MAIN RESULTS: Forty-seven trials (35,163 participants) fulfilled our inclusion criteria; 34 trials (33,793 participants) could be considered in the NMA (8 different treatment options). Bone mineral density We estimated that the bone mineral density of participants with no treatment/placebo measured as total T-score was -1.34. Evidence from the NMA (9 trials; 1166 participants) suggests that treatment with ibandronate (T-score -0.77; MD 0.57, 95% CI -0.05 to 1.19) may slightly increase bone mineral density (low certainty) and treatment with zoledronic acid (T-score -0.45; MD 0.89, 95% CI 0.62 to 1.16) probably slightly increases bone mineral density compared to no treatment/placebo (moderate certainty). Risedronate (T-score -1.08; MD 0.26, 95% CI -0.32 to 0.84) may result in little to no difference compared to no treatment/placebo (low certainty). We are uncertain whether alendronate (T-score 2.36; MD 3.70, 95% CI -2.01 to 9.41) increases bone mineral density compared to no treatment/placebo (very low certainty). Quality of life No quantitative analyses could be performed for quality of life, as only three studies reported this outcome. All three studies showed only minimal differences between the respective interventions examined. Overall fracture rate We estimated that 70 of 1000 participants with no treatment/placebo had fractures. Evidence from the NMA (16 trials; 19,492 participants) indicates that treatment with clodronate or ibandronate (42 of 1000; RR 0.60, 95% CI 0.39 to 0.92; 40 of 1000; RR 0.57, 95% CI 0.38 to 0.86, respectively) decreases the number of fractures compared to no treatment/placebo (high certainty). Denosumab or zoledronic acid (51 of 1000; RR 0.73, 95% CI 0.52 to 1.01; 55 of 1000; RR 0.79, 95% CI 0.56 to 1.11, respectively) probably slightly decreases the number of fractures; and risedronate (39 of 1000; RR 0.56, 95% CI 0.15 to 2.16) probably decreases the number of fractures compared to no treatment/placebo (moderate certainty). Pamidronate (106 of 1000; RR 1.52, 95% CI 0.75 to 3.06) probably increases the number of fractures compared to no treatment/placebo (moderate certainty). Overall survival We estimated that 920 of 1000 participants with no treatment/placebo survived overall. Evidence from the NMA (17 trials; 30,991 participants) suggests that clodronate (924 of 1000; HR 0.95, 95% CI 0.77 to 1.17), denosumab (927 of 1000; HR 0.91, 95% CI 0.69 to 1.21), ibandronate (915 of 1000; HR 1.06, 95% CI 0.83 to 1.34) and zoledronic acid (925 of 1000; HR 0.93, 95% CI 0.76 to 1.14) may result in little to no difference regarding overall survival compared to no treatment/placebo (low certainty). Additionally, we are uncertain whether pamidronate (905 of 1000; HR 1.20, 95% CI 0.81 to 1.78) decreases overall survival compared to no treatment/placebo (very low certainty). Osteonecrosis of the jaw We estimated that 1 of 1000 participants with no treatment/placebo developed osteonecrosis of the jaw. Evidence from the NMA (12 trials; 23,527 participants) suggests that denosumab (25 of 1000; RR 24.70, 95% CI 9.56 to 63.83), ibandronate (6 of 1000; RR 5.77, 95% CI 2.04 to 16.35) and zoledronic acid (9 of 1000; RR 9.41, 95% CI 3.54 to 24.99) probably increases the occurrence of osteonecrosis of the jaw compared to no treatment/placebo (moderate certainty). Additionally, clodronate (3 of 1000; RR 2.65, 95% CI 0.83 to 8.50) may increase the occurrence of osteonecrosis of the jaw compared to no treatment/placebo (low certainty). Renal impairment We estimated that 14 of 1000 participants with no treatment/placebo developed renal impairment. Evidence from the NMA (12 trials; 22,469 participants) suggests that ibandronate (28 of 1000; RR 1.98, 95% CI 1.01 to 3.88) probably increases the occurrence of renal impairment compared to no treatment/placebo (moderate certainty). Zoledronic acid (21 of 1000; RR 1.49, 95% CI 0.87 to 2.58) probably increases the occurrence of renal impairment while clodronate (12 of 1000; RR 0.88, 95% CI 0.55 to 1.39) and denosumab (11 of 1000; RR 0.80, 95% CI 0.54 to 1.19) probably results in little to no difference regarding the occurrence of renal impairment compared to no treatment/placebo (moderate certainty). AUTHORS' CONCLUSIONS: When considering bone-modifying agents for managing bone loss in women with early or locally advanced breast cancer, one has to balance between efficacy and safety. Our findings suggest that bisphosphonates (excluding alendronate and pamidronate) or denosumab compared to no treatment or placebo likely results in increased bone mineral density and reduced fracture rates. Our survival analysis that included pre and postmenopausal women showed little to no difference regarding overall survival. These treatments may lead to more adverse events. Therefore, forming an overall judgement of the best ranked bone-modifying agent is challenging. More head-to-head comparisons, especially comparing denosumab with any bisphosphonate, are needed to address gaps and validate the findings of this review.

Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements. We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS: We included 154 RCTs with a total of 7837 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 60 (2721 participants), and 48 (3029 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson's Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (60 studies; 2721 participants) suggests that dance and gait/balance/functional training probably have a moderate beneficial effect on the severity of motor signs (dance: mean difference (MD) -10.18, 95% confidence interval (CI) -14.87 to -5.36; gait/balance/functional training: MD -7.50, 95% CI -11.39 to -3.48; moderate confidence), and multi-domain training probably has a small beneficial effect on the severity of motor signs (MD -5.90, 95% CI -9.11 to -2.68; moderate confidence). The evidence also suggests that endurance, aqua-based, strength/resistance, and mind-body training might have a small beneficial effect on the severity of motor signs (endurance training: MD -5.76, 95% CI -9.78 to -1.74; aqua-based training: MD -5.09, 95% CI -10.45 to 0.40; strength/resistance training: MD -4.96, 95% CI -9.51 to -0.40; mind-body training: MD -3.62, 95% CI -7.24 to 0.00; low confidence). The evidence is very uncertain about the effects of "Lee Silverman Voice training BIG" (LSVT BIG) and flexibility training on the severity of motor signs (LSVT BIG: MD -6.70, 95% CI -16.48 to 3.08; flexibility training: MD 4.20, 95% CI -1.61 to 9.92; very low confidence). Quality of life The evidence from the NMA (48 studies; 3029 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -15.15, 95% CI -23.43 to -6.87; moderate confidence). The evidence also suggests that mind-body, gait/balance/functional, and multi-domain training and dance might have a small beneficial effect on QoL (mind-body training: MD -7.22, 95% CI -13.57 to -0.70; gait/balance/functional training: MD -6.17, 95% CI -10.75 to -1.59; multi-domain training: MD -5.29, 95% CI -9.51 to -1.06; dance: MD -3.88, 95% CI -10.92 to 3.00; low confidence). The evidence is very uncertain about the effects of gaming, strength/resistance, endurance, and flexibility training on QoL (gaming: MD -8.99, 95% CI -23.43 to 5.46; strength/resistance training: MD -6.70, 95% CI -12.86 to -0.35; endurance training: MD -6.52, 95% CI -13.74 to 0.88; flexibility training: MD 1.94, 95% CI -10.40 to 14.27; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

[Tc(NO)(Cp)(PPh3)Cl] and [Tc(NO)(Cp)(PPh3)(NCCH3)](PF6), and Their Reactions with Pyridine and Chalcogen Donors.

Reactions of the technetium(I) nitrosyl complex [Tc(NO)(Cp)(PPh3)Cl] with triphenylphosphine chalcogenides EPPh3 (E = O, S, Se), and Ag(PF6) in a CH2Cl2/MeOH mixture (v/v, 2/1) result in an exchange of the chlorido ligand and the formation of [Tc(NO)(Cp)(PPh3)(EPPh3)](PF6) compounds. The cationic acetonitrile complex [Tc(NO)(Cp)(PPh3)(NCCH3)]+ is formed when the reaction is conducted in NCCH3 without additional ligands. During the isolation of the corresponding PF6- salt a gradual decomposition of the anion was detected in the solvent mixture applied. The yields and the purity of the product increase when the BF4- salt is used instead. The acetonitrile ligand is bound remarkably strongly to technetium and exchange reactions readily proceed only with strong donors, such as pyridine or ligands with 'soft' donor atoms, such as the thioether thioxane. Substitutions on the cyclopentadienyl ring do not significantly influence the ligand exchange behavior of the starting material. 99Tc NMR spectroscopy is a valuable tool for the evaluation of reactions of the complexes of the present study. The extremely large chemical shift range of this method allows the ready detection of corresponding ligand exchange reactions. The observed 99Tc chemical shifts depend on the donor properties of the ligands. DFT calculations support the discussions about the experimental results and provide explanations for some of the unusual findings.

Can Physical Exercise Be Considered as a Promising Enhancer of Global Cognition in People with Parkinson's Disease? Results of a Systematic Review and Meta-Analysis.

Background: Physical exercise interventions are known to improve quality of life, motor and non-motor symptoms in people with Parkinson's disease (PD). However, systematic reviews and meta-analyses on cognitive outcomes are rare. Objective: To perform a systematic review and meta-analysis of physical exercise intervention effects compared with passive and active control groups (CGs) on global cognition in people with PD. Methods: A literature search was performed for randomized controlled trials (RCTs) on physical exercise interventions in PD using nine databases. We included RCTs reporting global cognition outcomes. A meta-analysis was performed using random-effects models and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Bias was assessed with the revised Cochrane Risk of Bias tool and the certainty of evidence was rated using the GRADE approach. Results: Seventeen studies (ten with passive, seven with active CGs) were included in the systematic review. Exercise interventions varied considerably between studies. The meta-analysis included nine studies with 236 people with PD (seven with passive, two with active CGs). The SMD was 0.33 (95% CI 0.00; 0.65) demonstrating a small effect (p = 0.05) in favor of physical exercise. Compared with passive CGs, physical exercise had a small non-significant effect (SMD = 0.22, 95% CI -0.14;0.58, p = 0.24). Compared with active CGs, physical exercise had a medium significant effect (SMD = 0.72, 95% CI 0.12;1.33, p = 0.02). Conclusions: Physical exercise may increase global cognition in people with PD, but the evidence is very uncertain. Further large-scale RCTs are needed to confirm this finding and to identify the most effective type of physical exercise for improving cognition.

Machine Learning Methods for Precision Dosing in Anticancer Drug Therapy: A Scoping Review.

INTRODUCTION: In the last decade, various Machine Learning techniques have been proposed aiming to individualise the dose of anticancer drugs mostly based on a presumed drug effect or measured effect biomarkers. The aim of this scoping review was to comprehensively summarise the research status on the use of Machine Learning for precision dosing in anticancer drug therapy. METHODS: This scoping review was conducted in accordance with the interim guidance by Cochrane and the Joanna Briggs Institute. We systematically searched the databases Medline (via PubMed), Embase and the Cochrane Library for research articles and reviews including results published after 2016. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: A total of 17 relevant studies was identified. In 12 of the included studies, Reinforcement Learning methods were used, including Classical, Deep, Double Deep and Conservative Q-Learning and Fuzzy Reinforcement Learning. Furthermore, classical Machine Learning methods were compared in terms of their performance and an artificial intelligence platform based on parabolic equations was used to guide dosing prospectively and retrospectively, albeit only in a limited number of patients. Due to the significantly different algorithm structures, a meaningful comparison between the various Machine Learning approaches was not possible. CONCLUSION: Overall, this review emphasises the clinical relevance of Machine Learning methods for anticancer drug dose optimisation, as many algorithms have shown promising results enabling model-free predictions with the potential to maximise efficacy and minimise toxicity when compared to standard protocols.

"There is only one motive fun." Perspectives of participants and providers of physical exercise for people with Parkinson's disease.

PURPOSE: To explore the perspectives of people with Parkinson's disease (PD) and exercise providers regarding facilitating factors, barriers, needs, and demands relating to physical exercise for people with PD. MATERIALS AND METHODS: Focus group discussions or telephone interviews of 30 people with PD (with or without an active sports history) and 13 providers were conducted and analyzed using structuring content analysis. RESULTS: Factors facilitating participation in physical exercise included motivation-enhancing elements (enjoyment, group training environment) and providers with sufficient qualifications in PD-specific training demands. Identified barriers were lack of motivation, physical limitations, poor service accessibility, and inadequate matching of intervention groups based on capability or age. Providers found it difficult to design and conduct group trainings for people with PD with varying physical limitations. Having an active sports history before PD-onset was described as generally beneficial, though a competitive mindset could lead to frustration. People with PD reported needing their physicians to provide better education regarding physical exercise. CONCLUSION: Enjoyment of physical exercise is a key aspect of maintaining physical activity engagement, which should be considered more in research and clinical practice. Developing qualifications for providers could help to broaden and enhance the dissemination of PD-specific exercise approaches. Physicians should be trained to encourage physical exercise.Implications for rehabilitationPhysicians should highlight the benefits and be knowledgeable regarding the availability of physical exercise interventions for people with PD.Additional physical exercise providers should become qualified to work with people with PD.The joyfulness of physical exercise interventions is a key aspect of maintaining physical activity engagement for people with PD.

Highly selective, reversible water activation by P,N-cooperativity in pyridyl-functionalized phosphinines.

Tetrapyridyl-functionalized phosphinines were prepared and structurally characterized. The donor-functionalized aromatic phosphorus heterocycles react highly selectively and even reversibly with water. Calculations reveal P,N-cooperativity for this process, with the flanking pyridyl groups serving to kinetically enhance the formal oxidative addition process of H2O to the low-coordinate phosphorus atom via H-bonding. Subsequent tautomerization forms 1,2-dihydrophosphinine derivatives, which can be quantitatively converted back to the phosphinine by applying vacuum, even at room temperature. This process can be repeated numerous times, without any sign of decomposition of the phosphinine. In the presence of CuI·SMe2, dimeric species of the type ([Cu2I2(phosphinine)]2) are formed, in which each phosphorus atom shows the less common µ2-bridging 2e--lone-pair-donation to two Cu(i)-centres. Our results demonstrate that fully unsaturated phosphorus heterocycles, containing reactive P[double bond, length as m-dash]C double bonds, are interesting candidates for the activation of E-H bonds, while the aromaticity of such compounds plays an appreciable role in the reversibility of the reaction, supported by NICS calculations.