Search

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The orientation map is one of the most well-studied functional maps of the visual cortex. However, results from the literature are of different qualities. Clear boundaries among different orientation domains and blurred uncertain distinctions were shown in different studies. These unclear imaging results will lead to an inaccuracy in depicting cortical structures, and the lack of consideration in experimental design will also lead to biased depictions of the cortical features. How we accurately define orientation domains will impact the entire field of research. In this study, we test how spatial frequency (SF), stimulus size, location, chromatic, and data processing methods affect the orientation functional maps (including a large area of dorsal V4, and parts of dorsal V1) acquired by intrinsic signal optical imaging. Our results indicate that, for large imaging fields, large grating stimuli with mixed SF components should be considered to acquire the orientation map. A diffusion model image enhancement based on the difference map could further improve the map quality. In addition, the similar outcomes of achromatic and chromatic gratings indicate two alternative types of afferents from LGN, pooling in V1 to generate cue-invariant orientation selectivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cutting edge advances in electrical visual cortical prosthetics have evoked perception of shapes, motion, and letters in the blind. Here, we present an alternative optical approach using pulsed infrared neural stimulation. To interface with dense arrays of cortical columns with submillimeter spatial precision, both linear array and 100-fiber bundle array optical fiber interfaces were devised. We deliver infrared stimulation through these arrays in anesthetized cat visual cortex and monitor effects by optical imaging in contralateral visual cortex. Infrared neural stimulation modulation of response to ongoing visual oriented gratings produce enhanced responses in orientation-matched domains and suppressed responses in non-matched domains, consistent with a known higher order integration mediated by callosal inputs. Controls include dynamically applied speeds, directions and patterns of multipoint stimulation. This provides groundwork for a distinct type of prosthetic targeted to maps of visual cortical columns., (© 2024. The Author(s).)

Our study focuses on the relationship between inflammatory biomarkers and hypertension among sedentary adults in the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We categorized 24,614 participants into two groups based on their daily sedentary time: 9607 individuals in the sedentary group (≥7 h) and 15,007 in the non-sedentary group (<7 h). We found that the sedentary group had a significantly higher prevalence of hypertension than the non-sedentary group. Using weighted multiple logistic regression and smoothing curves, we assessed the correlation between inflammatory biomarkers and hypertension among the sedentary adults. The odds ratios for hypertension were 1.92 for the monocyte to high-density lipoprotein ratio (MHR), 1.15 for the systemic inflammation response index (SIRI), and 1.19 for the natural logarithm of the systemic immune-inflammation index (lnSII), all showing nonlinear associations. Furthermore, a significant positive correlation was found between sedentary time and inflammatory biomarkers (MHR, SIRI, and lnSII). Our findings suggest that prolonged sedentary behavior in the US significantly increases hypertension risk, likely due to marked increases in inflammation markers., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Acute perimyocarditis is commonly preceded by viral illness and presents with non-specific complaints that can be a manifestation of serious cardiac complications such as arrhythmias and heart failure. While pericarditis is a known complication of thyrotoxicosis, termed "thyrotoxic pericarditis," concomitant new-onset perimyocarditis and Graves' disease, termed "thyro-pericarditis," has been reported. We present a case of thyro-pericarditis as the initial presentation of undiagnosed and untreated Graves' disease co-occurring with recent Coxsackievirus A and B infection. A 27-year-old male with a family history of undifferentiated hyperthyroidism presented with acute pleuritic chest pain and shortness of breath. Laboratory testing showed elevated cardiac troponin I with ST elevations and PR depressions on initial ECG. Left heart catheterization was normal, but transthoracic echocardiogram showed right ventricular systolic dysfunction and enlargement. Cardiac MRI demonstrated diffuse pericardial enhancement suggesting pericarditis. Thyroid function testing and thyroid ultrasound suggested auto-immune thyrotoxicosis. Serology noted abnormal Coxsackievirus A and B IgG antibody titers, suggesting prior infection. The patient was treated with colchicine, ibuprofen, methimazole, and metoprolol, with resolution of symptoms. Thyro-pericarditis is a rare concomitant presentation of both Graves' disease and myopericarditis, and it remains unknown whether there is an increased risk of adverse cardiac outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hsieh et al.)

Background: Sleep problems are common in adolescents and have detrimental impacts on physical and mental health and daily functioning. Evidence-based treatment like cognitive behaviour therapy for insomnia (CBT-I) is often hard to access, and adolescents may not engage in and adhere to longer, clinician-delivered interventions. Brief, self-guided, and accessible sleep interventions are needed., Objective: To explore the user experience of a prototype online self-help single session sleep intervention developed for adolescents., Methods: Eleven participants aged 17-19 years (8 females, 3 males) took part in online retrospective think-aloud interviews. Participants first completed the prototype intervention independently and were then shown the intervention page by page and asked to verbalise their thoughts and experiences. Transcripts were analyzed thematically., Results: Participants found the intervention helpful. Four themes were generated - 'Educative: Learning, but more fun', 'Effortless: Quicker and Easier', 'Personalization: Power of Choice', and 'Positivity: Just Good Vibes'. The theme 'Educative: Learning, but more fun' encompassed two sub-themes 'Opportunity to Learn' and 'Aesthetics and Learning'. These themes reflected participants' views that the intervention was educative, personalised, solution-oriented and easy to use, but could incorporate more graphics and visuals to aid in learning and could be made more effortless and positive through modifications to its design., Conclusions: Findings convey the importance of ensuring educative well-designed content, personalization, a positive tone, and ease of use while designing interventions targeting adolescents's sleep and mental health. They also indicate areas for further developing the intervention., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To explore barriers and facilitators that influence adherence to evidence-based guidelines for peripheral intravenous catheter care in different hospital wards., Design: Sequential explanatory mixedmethod study design, with qualitative data used to elaborate on quantitative findings., Method: Data were collected between March 2021 and March 2022 using the previously validated Peripheral Intravenous Catheter mini questionnaire (PIVC-miniQ) on each ward in a tertiary hospital in Norway. Survey completion was followed by individual interviews with nurses from selected wards. The Pillar Integration Process was used to integrate and analyse the quantitative and qualitative findings., Results: The PIVC-miniQ screening assessed 566 peripheral intravenous catheters in 448 patients in 41 wards, and we found variation between wards in the quality of care. Based on the quantitative variation, we interviewed 24 nurses on wards with either excellent or not as good quality. The integration of the quantitative and qualitative findings in the study enabled an understanding of factors that influence nurses' adherence to the care of peripheral venous catheters. One main theme and four subthemes emerged. The main finding was that ward culture affects education practice, and this was evident from four subthemes: (1) Deviation from best practice, (2) Gaps in education and clinical training, (3) Quality variation between wards and (4) The importance of supportive leadership., Conclusion: This mixed method study is the first study to explore reasons for variability in peripheral intravenous catheter quality across hospital wards. We found that ward culture was central to catheter quality, with evidence of deviations from best practice correlating with observed catheter complications. Ward culture also impacted nursing education, with the main responsibility for learning peripheral intravenous catheter management left to students' clinical training placements. Addressing this educational gap and fostering supportive leadership, including champions, will likely improve peripheral intravenous catheter care and patient safety., Implications for the Profession And/or Patient Care: Nurses learn good peripheral intravenous catheter care in wards with supportive leaders and champions. This implies that the quality of nursing practice and patient outcomes are situational. Nurses need a strengthened emphasis on peripheral catheter quality in the undergraduate curriculum, and nurse leaders must emphasize the quality of catheter care in their wards., Impact: The study findings impact nurse leaders who must commit to quality and safety outcomes by appointing and supporting local ward champions for promoting peripheral intravenous catheter care. This also impacts nursing education providers, as the emphasis on catheter care must be strengthened in the undergraduate nursing curriculum and continually reinforced in the hospital environment, particularly when guidelines are updated., Reporting Method: The study adhered to the Good Reporting of A Mixed Method Study (GRAMM)., Patient or Public Contribution: A patient representative has been involved in planning this study., (© 2024 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Background: There has been a trend to shift from a 155° and 145° neck-shaft-angle (NSA) to a more "anatomical" reverse shoulder arthroplasty with less distalization and a 135° NSA. Multiple studies have shown that a 135° NSA is beneficial for motion. There are some concerns about primary implant stability with a 135° NSA. When instability is detected, increasing the tension with thicker inlays or changing the NSA to 145° are possible solutions. A retentive 135° (Ret135) inlay may be an alternative to avoiding increased distalization; however, retentive liners are widely regarded as salvage options reducing range of motion (ROM) and avoided by most surgeons. The hypothesis of this study was that a retentive 135° insert of the tested implant system may not have drawbacks for impingement-free ROM compared to a standard 145° insert (Sta145)., Methods: In this computer model study, 22 computed tomographic scans (11 males/11 females) were used to create models with a constant humeral stem (Perform/Stryker) and +3 mm lateralized baseplate +36 mm glenosphere for females and +6 mm lateralized baseplate +39 mm glenosphere for males using Blueprint software (Imascap, Brest, France). A Ret135, standard 135° (Sta135), and Sta145 (+10°) insert were compared for adduction (ADD), extension (EXT), external rotation (ER), and internal rotation (IR) all with the arm at the side as well as for combined IR (CIR = EXT + IR) and combined notching relevant (CNR) ROM (EXT + ER + IR + ADD)., Results: Sta135 showed significantly better ROM for ER, IR, ADD, EXT, CNR ROM, and CIR compared to Ret135 ( P  < .05) and significantly better EXT and ADD compared to Sta145 ( P  < .0001). Comparison of Ret135 and Sta145 showed equivalent ROM performance, which was slightly better but nonsignificant for ADD ( P  = .16), EXT ( P  = .31), CNR ROM ( P  = .7), and CIR ( P  = .54) in favor of Ret135. Isolated IR ( P  = .39) and ER ( P  = .32) were slightly better but nonsignificant in favor of a Sta145., Conclusion: For this implant system tested in a computer model, a 135° standard liner offers the best ROM. A 135° retentive liner maintains at least equivalent CIR and motion to prevent notching compared to a standard 145° liner. 135° retentive liners are more than salvage options and may help to prevent distalization and overtensioning by increased liner thickness., (© 2024 The Authors.)

The primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal (BA), lateral (LA), and central (CeA) nuclei, respectively. Based on recent electrophysiological evidence suggesting mesoscale (millimeters-scale) nature of intra-amygdala functional organization, we have investigated the connectivity of these nuclei using Infrared Neural Stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7T functional Magnetic Resonance Imaging (INS-fMRI). Stimulation of multiple sites within amygdala of single individuals evoked 'mesoscale functional connectivity maps', allowing comparison of BA, LA and CeA connected brainwide networks. This revealed a mesoscale nature of connected sites, complementary spatial patterns of functional connectivity, and topographic relationships of nucleus-specific connections. Our data reveal a functional architecture of systematically organized brainwide networks mediating sensory, cognitive, and autonomic influences from the amygdala., Competing Interests: Competing interests: Authors declare that they have no competing interests.

Infrared neural stimulation (INS) delivered via short pulse trains is an innovative tool that has potential for us use for studying brain function and circuitry, brain machine interface, and clinical use. The prevailing mechanism for INS involves the conversion of light energy into thermal transients, leading to neuronal membrane depolarization. Due to the potential risks of thermal damage, it is crucial to ensure that the resulting local temperature increases are within non-damaging limits for brain tissues. Previous studies have estimated damage thresholds using histological methods and have modeled thermal effects based on peripheral nerves. However, additional quantitative measurements and modeling studies are needed for the central nervous system. Here, we performed 7 T MRI thermometry on ex vivo rat brains following the delivery of infrared pulse trains at five different intensities from 0.1-1.0 J/cm 2 (each pulse train 1,875 nm, 25 us/pulse, 200 Hz, 0.5 s duration, delivered through 200 µm fiber). Additionally, we utilized the General BioHeat Transfer Model (GBHTM) to simulate local temperature changes in perfused brain tissues while delivering these laser energies to tissue (with optical parameters of human skin) via three different sizes of optical fibers at five energy intensities. The simulation results clearly demonstrate that a 0.5 second INS pulse train induces an increase followed by an immediate drop in temperature at stimulation offset. The delivery of multiple pulse trains with 2.5 s interstimulus interval (ISI) leads to rising temperatures that plateau. Both thermometry and modeling results show that, using parameters that are commonly used in biological applications (200 µm diameter fiber, 0.1-1.0 J/cm 2 ), the final temperature increase at the end of the 60 sec stimuli duration does not exceed 1°C with stimulation values of 0.1-0.5 J/cm 2 and does not exceed 2°C with stimulation values of up to 1.0 J/cm 2 . Thus, the maximum temperature rise is consistent with the thermal damage threshold reported in previous studies. This study provides a quantitative evaluation of the temperature changes induced by INS, suggesting that existing practices pose minimal major safety concerns for biological tissues., Competing Interests: The Authors declare no Competing Financial or Non-Financial Interests., (© 2024 Optica Publishing Group.)

Objective: A systematic review and meta-analysis was conducted to examine associations between attempts to cope with stressors through the two facets of emotional approach coping (EAC; i.e., processing and expressing stressor-related emotions) and indicators of physical and mental health., Method: EBSCO databases including MEDLINE, PsycINFO, and Cochrane Collections were searched from inception to November 2022. In all, 86 studies were included in a meta-analytic evaluation using a random-effects model and meta-regression analysis., Results: EAC was associated with better overall health ( r = .05; p = .04; 95% confidence interval = [.003, .10]). Emotional expression (EE) and emotional processing (EP) also were positively associated with better overall health, although these relationships were not statistically significant. In meta-regressions examining specific health domains, EAC was linked to better health in biological/physiological, physical, and resilience-related psychological adjustment domains, as well as to worse outcomes in the risk-related psychological adjustment and mental/emotional distress domains. Results for EE and EP mirrored this pattern; however, only EP was associated with more engagement in health-promoting behaviors., Conclusions: Coping with stressors through emotional approach appears to be associated with better mental and physical health, with some observed differences for EE and EP. The literature on EAC and health is marked by heterogeneity across study methodologies and measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Significance: Pulsed infrared neural stimulation (INS, 1875 nm) is an emerging neurostimulation technology that delivers focal pulsed heat to activate functionally specific mesoscale networks and holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in cerebral cortex., Aim: Estimates of summed population neuronal response time courses provide a potential basis for neural and hemodynamic signals described in other studies., Approach: Using two-photon calcium imaging in mouse somatosensory cortex, we have examined the effect of INS pulse train application on hSyn neurons and mDlx neurons tagged with GCaMP6s., Results: We find that, in anesthetized mice, each INS pulse train reliably induces robust response in hSyn neurons exhibiting positive going responses. Surprisingly, mDlx neurons exhibit negative going responses. Quantification using the index of correlation illustrates responses are reproducible, intensity-dependent, and focal. Also, a contralateral activation is observed when INS applied., Conclusions: In sum, the population of neurons stimulated by INS includes both hSyn and mDlx neurons; within a range of stimulation intensities, this leads to overall excitation in the stimulated population, leading to the previously observed activations at distant post-synaptic sites., (© 2024 The Authors.)

Our objectives were to quantify geographical disparities in otolaryngology care access with respect to American Indian (AI) populations and to identify gaps in care. Although increased incidence and mortality rates of ear, nose, and throat (ENT) conditions in AI populations are well documented, few studies address factors contributing to these differential outcomes. We conducted a cross-sectional study of US states with AI areas that either met the population threshold for the American Community Survey annual estimate or annual supplemental estimate. A 2-tailed t test was used to compare the geographic distribution of ENT providers practicing within AI areas against non-AI areas, showing a statistically significant difference ( P  < .001) in the concentration of providers (0.409 vs 2.233 providers per 100,000 patients). To our knowledge, this is the first study to explore geographic barriers contributing to AI disparities within otolaryngology., Competing Interests: None., (© 2024 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

In human and nonhuman primate brains, columnar (mesoscale) organization has been demonstrated to underlie both lower and higher order aspects of visual information processing. Previous studies have focused on identifying functional preferences of mesoscale domains in specific areas; but there has been little understanding of how mesoscale domains may cooperatively respond to single visual stimuli across dorsal and ventral pathways. Here, we have developed ultrahigh-field 7 T fMRI methods to enable simultaneous mapping, in individual macaque monkeys, of response in both dorsal and ventral pathways to single simple color and motion stimuli. We provide the first evidence that anatomical V2 cytochrome oxidase-stained stripes are well aligned with fMRI maps of V2 stripes, settling a long-standing controversy. In the ventral pathway, a systematic array of paired color and luminance processing domains across V4 was revealed, suggesting a novel organization for surface information processing. In the dorsal pathway, in addition to high quality motion direction maps of MT, MST and V3A, alternating color and motion direction domains in V3 are revealed. As well, submillimeter motion domains were observed in peripheral LIPd and LIPv. In sum, our study provides a novel global snapshot of how mesoscale networks in the ventral and dorsal visual pathways form the organizational basis of visual objection recognition and vision for action., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Keshan disease (KD) is a type of endemic cardiomyopathy with an unknown cause. It is primarily found in areas in China with low selenium levels, from northeast to southwest. The nutritional biogeochemical etiology hypothesis suggests that selenium deficiency is a major factor in KD development. Selenium is important in removing free radicals and protecting cells and tissues from peroxide-induced damage. Thus, low environmental selenium may affect the selenium level within the human body, and selenium level differences are commonly observed between healthy people in KD and nonKD areas. From the 1970s to the 1990s, China successfully reduced KD incidence in endemic KD areas through a selenium supplementation program. After years of implementing prevention and control measures, the selenium level of the population in the KD areas has gradually increased, and the prevalence of KD in China has remained low and stable in recent years. Currently, the pathogenesis of KD remains vague, and the effect of selenium supplementation on the prognosis of KD still needs further study. This paper comprehensively reviews selenium deficiency and its connection to KD. Thus, this study aims to offer novel ideas and directions to effectively prevent and treat KD in light of the current situation.

Background: In reverse shoulder arthroplasty (RSA), the ideal combination of baseplate lateralization (BL), glenosphere size (GS), and glenosphere overhang (GOH) with a commonly used 145° neck shaft angle (NSA) is unclear. This is the first study evaluating correlations of body height (BH), humeral head size (HS), glenoid height (GH), and association of gender with best glenoid configurations for range of motion (ROM) maintaining anatomic lateralization (aLAT) for optimized muscle length in 145° and less distalized 135° RSA., Methods: In this computer model study, 22 computed tomographies without joint narrowing were analyzed (11 male/female). A standardized semi-inlay 145° platform stem was combined with 20 glenoid configurations (baseplate [B] 25, 25 + 3/+6 lateralized [l], 29, 29 + 3/6l combined with glenosphere 36, 36 + 2 eccentric [e], 36 + 3l, 39, 39 + 3e, 39 + 3l , 42, 42 + 4e). Abduction-adduction, flexion-extension, external rotation-internal rotation, total ROM (TROM), and total notching relevant (TNR) ROM were computed, best TROM models respecting aLAT (-1 mm to +1 mm) and HS/GH recorded. Second, the 145° models (Ascend Flex stem; Stryker, Kalamazoo, MI, USA) were converted and compared to a 135° inlay RSA (New Perform stem; Stryker, Kalamazoo, MI, USA) maintaining GOH (6.5-7 mm) and aLAT., Results: Best 145° models had eccentric glenospheres (mean BL: 3.5 mm, GOH 8.8 mm, GS 38.1 mm, distalization 23 mm). The 135° models had concentric glenospheres, mean BL 3.8 mm, GOH 6.9 mm, GS 39.7 mm, and distalization 14.1 mm. HS showed the strongest positive correlation with BL in 145° and 135° models (0.65/0.79). Despite reduced GOH in smaller females with a 135° NSA, adduction, external rotation, extension, TNR ROM, and TROM were significantly increased ( P  = .02, P  = .005, P  = .005, P  = .004, P  = .003), abduction however reduced ( P  = .02). The same trends were seen for males., Conclusion: HS is a practical measure in surgery or preoperatively, and the strong positive correlation with BL is a useful planning aid. Despite reduction of GOH, conversion to a less distalized 135° NSAinlay design is powerful to maintain and even significantly increase all components of TNR ROM (extension/external rotation/adduction) in small females with the drawback of reduced abduction which may however be compensated by scapula motion. Lateralization with a less distalized 135° RSA optimizes muscle length, may facilitate subscapularis repair, and maintains highest rigid body motion., (© 2023 The Authors.)

Purpose: Do cancer survivors experience positive changes (i.e., posttraumatic growth; PTG) resulting in better quality of life? The issue has yet to yield consistent notions. This longitudinal study extends the literature on the role of PTG by examining the curvilinear relationship between PTG and Health-Related Quality of Life (HRQoL), and explored whether PTG predicts subsequent HRQoL in a quadratic relationship across 2 years following surgery., Methods: Women with breast cancer (N = 359; Mage = 47.5) were assessed at five waves over two years. On every measurement occasion, PTG measured by the posttraumatic growth inventory and HRQoL measured by SF-36 were assessed. The five waves reflect major medical demands and related challenges in the breast cancer trajectory, in which 1-day, 3 months, 6 months, 12 months, and 24 months after surgery were adopted as the survey timing. In a series of hierarchical linear modeling (HLM) analyses, the time-lagged predictions of PTG (i.e., linear, quadratic) on HRQoL were examined, controlling demographic and medical covariates., Results: The results revealed that the quadratic term of PTG consistently significantly predicted physical and mental health quality of life (PCS and MCS), while the linear term of PTG did not significantly predict PCS or MCS., Conclusion: With multi-wave longitudinal data, this study demonstrated that the relationship between PTG and HRQoL is curvilinear, and this finding extends to PTG's prediction of subsequent HRQoL. The quadratic relationship has critical implications for clinical assessment and intervention. Details are discussed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Interaction between the inferotemporal (ITC) and prefrontal (PFC) cortices is critical for retrieving information from memory and maintaining it in working memory. Neural oscillations provide a mechanism for communication between brain regions. However, it remains unknown how information flow via neural oscillations is functionally organized in these cortices during these processes. In this study, we apply Granger causality analysis to electrocorticographic signals from both cortices of monkeys performing visual association tasks to map information flow. Our results reveal regions within the ITC where information flow to and from the PFC increases via specific frequency oscillations to form clusters during memory retrieval and maintenance. Theta-band information flow in both directions increases in similar regions in both cortices, suggesting reciprocal information exchange in those regions. These findings suggest that specific subregions function as nodes in the memory information-processing network between the ITC and the PFC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Combining multimodal approaches with functional magnetic resonance imaging (fMRI) has catapulted the research on brain circuitries of non-human primates (NHPs) into a new era. However, many studies are constrained by a lack of appropriate RF coils. In this study, a single loop transmit and 16-channel receive array coil was constructed for brain imaging of macaques at 7 Tesla (7 T). The 16 receive channels were mounted on a 3D-printed helmet-shaped form closely fitting the macaque head, with fourteen openings arranged for multimodal devices around the cortical regions. Coil performance was evaluated by quantifying and comparing signal-to-noise ratio (SNR) maps, noise correlations, g-factor maps and flip-angle maps with a 28-channel commercial knee coil. The in vivo results suggested that the macaque coil has higher SNR in cortical regions and better acceleration ability in parallel imaging, which may benefit revealing mesoscale organizations in the brain., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Systematic understanding of patients' unmet needs is essential for providing effective supportive care. This study sought to compare the unmet needs of patients with cancer identified by health care providers (HCPs) among four major healthcare systems., Methods: HCPs (n = 247) participated in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey, evaluating their patients' unmet needs. The country of HCPs was grouped into four major healthcare systems: Beveridge model, Bismarck model, National Health Insurance model, and out-of-pocket model., Results: Most HCPs were from countries with the Bismarck model. Substantial levels (> 50%) of unmet needs in all domains are reported across the four healthcare systems. Pediatric patients/survivors living in countries under out-of-pocket healthcare model were evaluated to have less unmet needs for managing decline in physical or cognitive functioning and insomnia/sleep difficulty/fatigue, than those in countries under Beveridge, Bismarck, and National Health Insurance models. Moreover, middle-aged patients/survivors under Beveridge and National Health Insurance models were likely to have greater unmet needs for dealing with cancer-related financial concerns than those under Bismarck model., Conclusion: This study provides valuable insights into the unmet needs of patients with cancer in different healthcare systems, highlighting the significance of targeted interventions to address the unique needs of patients across diverse healthcare systems. Further investigation is warranted to identify the system factors associated with patients' unmet needs, enabling the development of effective healthcare policies and interventions to comprehensively address the multifaceted needs of patients with cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Young adult testicular cancer survivors experience adverse impacts after treatment. We developed Goal-focused Emotion-regulation Therapy (GET) to improve distress symptoms, emotion regulation, and goal navigation skills., Purpose: This pilot study examined GET versus an active control intervention in young adult survivors of testicular cancer., Methods: Seventy-five eligible survivors treated with chemotherapy were randomized to receive GET or Individual Supportive Listening (ISL). Study acceptability, engagement, and tolerability were examined, and intervention fidelity and therapeutic alliance were compared between arms. Preliminary efficacy was evaluated by effect sizes for between-group changes in primary (anxiety and depressive symptoms) and secondary (career confusion, goal navigation, and emotion regulation) outcomes from baseline to immediately and 3-month post-intervention., Results: Among the 38 men randomized to GET, 81.1% completed all study sessions compared with 82.4% of the 37 men assigned to ISL. Fidelity to the intervention was 87% in GET. Therapeutic alliance wassignificantly higher among those receiving GET versus ISL. Participants exhibited a medium group-by-time effect size with greater reductions in depressive (d = 0.45) and anxiety (d = 0.29) symptoms for those in GET versus ISL, with a similar pattern at 3 months for depressive (d = 0.46) and anxiety (d = 0.46) symptoms., Conclusions: GET is a feasible and acceptable intervention for reducing adverse outcomes after testicular cancer for young adults. Observed effect sizes preliminarily suggest meaningful change, though should be interpreted with caution in small samples. GET may be a developmentally-matched behavioral approach to improve psychosocial function in this cancer group., Clinical Trial Information: Clinicaltrials.gov, NCT04150848. Registered on October 28, 2019., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

TGFβ signaling is associated with non-response to immune checkpoint blockade in patients with advanced cancers, particularly in the immune-excluded phenotype. While previous work demonstrates that converting tumors from excluded to inflamed phenotypes requires attenuation of PD-L1 and TGFβ signaling, the underlying cellular mechanisms remain unclear. Here, we show that TGFβ and PD-L1 restrain intratumoral stem cell-like CD8 T cell (T SCL ) expansion and replacement of progenitor-exhausted and dysfunctional CD8 T cells with non-exhausted T effector cells in the EMT6 tumor model in female mice. Upon combined TGFβ/PD-L1 blockade IFNγ hi CD8 T effector cells show enhanced motility and accumulate in the tumor. Ensuing IFNγ signaling transforms myeloid, stromal, and tumor niches to yield an immune-supportive ecosystem. Blocking IFNγ abolishes the anti-PD-L1/anti-TGFβ therapy efficacy. Our data suggest that TGFβ works with PD-L1 to prevent T SCL expansion and replacement of exhausted CD8 T cells, thereby maintaining the T cell compartment in a dysfunctional state., (© 2023. Springer Nature Limited.)

Objective: Blood-oxygen-level-dependent functional MRI allows to investigte neural activities and connectivity. While the non-human primate plays an essential role in neuroscience research, multimodal methods combining functional MRI with other neuroimaging and neuromodulation enable us to understand the brain network at multiple scales., Approach: In this study, a tight-fitting helmet-shape receive array with a single transmit loop for anesthetized macaque brain MRI at 7T was fabricated with four openings constructed in the coil housing to accommodate multimodal devices, and the coil performance was quantitatively evaluated and compared to a commercial knee coil. In addition, experiments over three macaques with infrared neural stimulation (INS), focused ultrasound stimulation (FUS), and transcranial direct current stimulation (tDCS) were conducted., Main Results: The RF coil showed higher transmit efficiency, comparable homogeneity, improved SNR and enlarged signal coverage over the macaque brain. Infrared neural stimulation was applied to the amygdala in deep brain region, and activations in stimulation sites and connected sites were detected, with the connectivity consistent with anatomical information. Focused ultrasound stimulation was applied to the left visual cortex, and activations were acquired along the ultrasound traveling path, with all time course curves consistent with pre-designed paradigms. The existence of transcranial direct current stimulation electrodes brought no interference to the RF system, as evidenced through high-resolution MPRAGE structure images., Significance: This pilot study reveals the feasibility for brain investigation at multiple spatiotemporal scales, which may advance our understanding in dynamic brain networks., Competing Interests: Declaration of Competing Interest The Authors declare no Competing Financial or Non-Financial Interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Human speech and animal vocalizations are important for social communication and animal survival. Neurons in the auditory pathway are responsive to a range of sounds, from elementary sound features to complex acoustic sounds. For social communication, responses to distinct patterns of vocalization are usually highly specific to an individual conspecific call, in some species. This includes the specificity of sound patterns and embedded biological information. We conducted single-unit recordings in the amygdala of awake marmosets and presented calls used in marmoset communication, calls of other species and calls from specific marmoset individuals. We found that some neurons (47/262) in the amygdala distinguished 'Phee' calls from vocalizations of other animals and other types of marmoset vocalizations. Interestingly, a subset of Phee-responsive neurons (22/47) also exhibited selectivity to one out of the three Phees from two different 'caller' marmosets. Our findings suggest that, while it has traditionally been considered the key structure in the limbic system, the amygdala also represents a critical stage of socially relevant auditory perceptual processing., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

The field of brain machine interface has long sought a technology for brainwide interaction. In this issue of Neuron, Kim et al. 1 present a novel method for dynamic, patterned, and precise optogenetic stimulation of mouse cortex in ultra-high-field MRI that portends such an interface., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recent studies have highlighted the importance of understanding the architecture and function of microvasculature, and dysfunction of these microvessels may underlie neurodegenerative disease. Here, we utilize a high-precision ultrafast laser-induced photothrombosis (PLP) method to occlude single capillaries and then quantitatively study the effects on vasodynamics and surrounding neurons. Analysis of the microvascular architecture and hemodynamics after single-capillary occlusion reveals distinct changes upstream vs. downstream branches, which shows rapid regional flow redistribution and local downstream blood-brain barrier (BBB) leakage. Focal ischemia via capillary occlusions surrounding labeled target neurons induces dramatic and rapid lamina-specific changes in neuronal dendritic architecture. Further, we find that micro-occlusion at two different depths within the same vascular arbor results in distinct effects on flow profiles in layers 2/3 vs layer 4. The current results reveal laminar-scale regulation distinctions in microinfarct response and raise the possibility that relatively greater impacts on microvascular function contribute to cognitive decline in neurodegenerative disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Targeted optical neural stimulation comprises infrared neural stimulation and optogenetics, which affect the nervous system through induced thermal transients and activation of light-sensitive proteins, respectively. The main advantage of this pair of optical tools is high functional selectivity, which conventional electrical stimulation lacks. Over the past 15 years, the mechanism, safety, and feasibility of optical stimulation techniques have undergone continuous investigation and development. When combined with other methods like optical imaging and high-field functional magnetic resonance imaging, the translation of optical stimulation to clinical practice adds high value. We review the theoretical foundations and current state of optical stimulation, with a particular focus on infrared neural stimulation as a potential bridge linking optical stimulation to personalized medicine.

The pulvinar in the macaque monkey contains three divisions: the medial pulvinar (PM), the lateral pulvinar (PL), and the inferior pulvinar (PI). Anatomical studies have shown that connections of PM are preferentially distributed to higher association areas, those of PL are biased toward the ventral visual pathway, and those of PI are biased with the dorsal visual pathway. To study functional connections of the pulvinar at mesoscale, we used a novel method called INS-fMRI (infrared neural stimulation and functional magnetic resonance imaging). This method permits studies and comparisons of multiple pulvinar networks within single animals. As previously revealed, stimulations of different sites in PL and PI produced topographically organized focal activations in visual areas V1, V2, and V3. In contrast, PM stimulation elicited little or diffuse response. The relative activations of areas V1, V2, V3A, V3d, V3v, V4, MT, and MST revealed that connections of PL are biased to ventral pathway areas, and those of PI are biased to dorsal areas. Different statistical values of activated blood-oxygen-level-dependent responses produced the same center of activation, indicating stability of connectivity; it also suggests possible dynamics of broad to focal responses from single stimulation sites. These results demonstrate that infrared neural stimulation-induced connectivity is largely consistent with previous anatomical connectivity studies, thereby demonstrating validity of our novel method. In addition, it suggests additional interpretations of functional connectivity to complement anatomical studies., (© 2023 Wiley Periodicals LLC.)

Background: Modulation of brain circuits by electrical stimulation has led to exciting and powerful therapies for diseases such as Parkinson's. Because human brain organization is based in mesoscale (millimeter-scale) functional nodes, having a method that can selectively target such nodes could enable more precise, functionally specific stimulation therapies. Infrared Neural Stimulation (INS) is an emerging stimulation technology that stimulates neural tissue via delivery of tiny heat pulses. In nonhuman primates, this optical method provides focal intensity-dependent stimulation of the brain without tissue damage. However, whether INS application to the human central nervous system (CNS) is similarly effective is unknown., Objective: To examine the effectiveness of INS on human cerebral cortex in intraoperative setting and to evaluate INS damage threshholds., Methods: Five epileptic subjects undergoing standard lobectomy for epilepsy consented to this study. Cortical response to INS was assessed by intrinsic signal optical imaging (OI, a method that detects changes in tissue reflectance due to neuronal activity). A custom integrated INS and OI system was developed specifically for short-duration INS and OI acquisition during surgical procedures. Single pulse trains of INS with intensities from 0.2 to 0.8 J/cm 2 were delivered to the somatosensory cortex and responses were recorded via optical imaging. Following tissue resection, histological analysis was conducted to evaluate damage threshholds., Results: As assessed by OI, and similar to results in monkeys, INS induced responses in human cortex were highly focal (millimeter sized) and led to relative suppression of nearby cortical sites. Intensity dependence was observed at both stimulated and functionally connected sites. Histological analysis of INS-stimulated human cortical tissue provided damage threshold estimates., Conclusion: This is the first study demonstrating application of INS to human CNS and shows feasibility for stimulating single cortical nodes and associated sites and provided INS damage threshold estimates for cortical tissue. Our results suggest that INS is a promising tool for stimulation of functionally selective mesoscale circuits in the human brain, and may lead to advances in the future of precision medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart 1-3 . However, whether an increased heart rate might itself induce anxiety or fear responses is unclear 3-8 . Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain 9 . Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour., (© 2023. The Author(s).)

A detailed overview of the basic science and clinical literature reporting on the challenges for the optimization of reverse shoulder arthroplasty (RSA) is presented in two review articles. Part I looks at (I) external rotation and extension, (II) internal rotation and the analysis and discussion of the interplay of different factors influencing these challenges. In part II, we focus on (III) the conservation of sufficient subacromial and coracohumeral space, (IV) scapular posture and (V) moment arms and muscle tensioning. There is a need to define the criteria and algorithms for planning and execution of optimized, balanced RSA to improve the range of motion, function and longevity whilst minimizing complications. For an optimized RSA with the highest function, it is important not to overlook any of these challenges. This summary may be used as an aide memoire for RSA planning.

As science and technology evolve, there is an increasing need for promotion of international scientific exchange. Collaborations, while offering substantial opportunities for scientists and benefit to society, also present challenges for those working with animal models, such as non-human primates (NHPs). Diversity in regulation of animal research is sometimes mistaken for the absence of common international welfare standards. Here, the ethical and regulatory protocols for 13 countries that have guidelines in place for biomedical research involving NHPs were assessed with a focus on neuroscience. Review of the variability and similarity in trans-national NHP welfare regulations extended to countries in Asia, Europe and North America. A tabulated resource was established to advance solution-oriented discussions and scientific collaborations across borders. Our aim is to better inform the public and other stakeholders. Through cooperative efforts to identify and analyze information with reference to evidence-based discussion, the proposed key ingredients may help to shape and support a more informed, open framework. This framework and resource can be expanded further for biomedical research in other countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In part II of this comprehensive review on the optimization of reverse shoulder arthroplasty (RSA), we focus on three other challenges: 1. "Conservation of sufficient subacromial and coracohumeral space"; 2. "Scapular posture"; and 3. "Moment arms and muscle tensioning". This paper follows a detailed review of the basic science and clinical literature of the challenges in part I: 1. "External rotation and extension" and 2. "Internal rotation". "Conservation of sufficient subacromial and coracohumeral space" and "Scapular posture" may have a significant impact on the passive and active function of RSA. Understanding the implications of "Moment arms and muscle tensioning" is essential to optimize active force generation and RSA performance. An awareness and understanding of the challenges of the optimization of RSA help surgeons prevent complications and improve RSA function and raise further research questions for ongoing study.

We sought to determine differences by low- and middle- income countries (Brazil, Romania, and Turkiye) on the degree to which health care providers (HCPs) note unmet needs among patients with cancer ( N  = 741). HCPs endorsed sexuality/intimacy and financial concerns as the most common. Investigating age differences in unmet needs between Brazil and Turkiye, were that should be targeted by. Results revealed that unmet needs to manage emotional distress were higher among older patients in Turkiye, whereas unmet needs to manage insomnia/fatigue were higher among pediatric patients in Brazil. Findings may guide the development of programs to address unmet needs among patients.

Spatial frequency (SF) is an important attribute in the visual scene and is a defining feature of visual processing channels. However, there remain many unsolved questions about how extrastriate areas in primate visual cortex code this fundamental information. Here, using intrinsic signal optical imaging in visual areas of V2 and V4 of macaque monkeys, we quantify the relationship between SF maps and (1) visual topography and (2) color and orientation maps. We find that in orientation regions, low to high SF is mapped orthogonally to orientation; in color regions, which are reported to contain orthogonal axes of color and lightness, low SFs tend to be represented more frequently than high SFs. This supports a population-based SF fluctuation related to the 'color/orientation' organizations. We propose a generalized hypercolumn model across cortical areas, comprised of two orthogonal parameters with additional parameters., Competing Interests: YZ, KS, JH, AR No competing interests declared, (© 2023, Zhang et al.)

The cerebrovasculature plays an essential role in neurovascular and homeostatic functions in health and disease conditions. Many efforts have been made for developing vascular thrombosis methods to study vascular dysfunction in vivo, while technical challenges remain, such as accuracy and depth-selectivity to target a single vessel in the cerebral cortex. Herein, this paper first demonstrates the evaluation and quantification of the feasibility and effects of Rose Bengal (RB)-induced photothrombosis with 720-1070 nm ultrafast lasers in a raster scan. A flexible and reproducible approach is then proposed to employ a 1070 nm ultrafast laser with a spiral scan for producing RB-induced occlusion, which is described as precision ultrafast laser-induced photothrombosis (PLP). Combine with two-photon microscopy imaging, this PLP displays highly precise and fast occlusion induction of various vessel types, sizes, and depths, which enhances the precision and power of the photothrombosis protocol. Overall, the PLP method provides a real-time, practical, precise, and depth-selected single-vessel photothrombosis technology in the cerebral cortex with commercially available optical equipment, which is crucial for exploring brain vascular function with high spatial-temporal resolution in the brain., (© 2022 The Authors. Small Methods published by Wiley-VCH GmbH.)

Purpose: This international study aimed to compare healthcare professionals' perspectives on the unmet needs of their cancer patients with those of family caregivers and to investigate the degree to which patients' age group moderates the associations., Methods: Healthcare professionals involved in the care for cancer patients and their family caregivers were invited to participate in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey. A total of 397 healthcare professionals from 34 countries provided valid study data. The participants evaluated whether the unmet need was the same for all age groups of patients and the degree of their patients' needs not being met per patients' age group. They evaluated the same questions for family caregivers., Results: Patients' unmet needs in medical care were evaluated as greater than those of caregivers across all age groups. On the other hand, pediatric patients' unmet needs for spiritual concerns, sexuality/intimacy, and insomnia/fatigue were evaluated as greater than those of caregivers, whereas adolescent and young adult patients' unmet needs for symptom management were greater than those of caregivers. Patients' other unmet needs were evaluated as comparable with those of caregivers regardless of age groups., Conclusion: The findings provide insights how best healthcare providers stratify resources to address the unmet needs of patients and caregivers by the patients' age. Development of systematic assessment of unmet needs and provision of interventions tailored for patients' lifespan to address the unmet needs of cancer patients, and caregivers are warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we investigated the composition of appendicoliths using laser ablation inductively coupled plasma mass spectroscopy, gas chromatography, polarized light microscopy, X-ray crystallography and protein mass spectroscopy. Forty-eight elements, 32 fatty acids and 109 human proteins were identified within the appendicoliths. The most common elements found in appendicoliths are calcium and phosphorus, 11.0 ± 6.0 and 8.2 ± 4.2% weight, respectively. Palmitic acid (29.7%) and stearate (21.3%) are the most common fatty acids. Some stearate is found in crystalline form-identifiable by polarized light microscopy and confirmable by X-ray crystallography. Appendicoliths have an increased ratio of omega-6 to omega-3 fatty acids (ratio 22:1). Analysis of 16 proteins common to the appendicoliths analyzed showed antioxidant activity and neutrophil functions (e.g. activation and degranulation) to be the most highly enriched pathways. Considered together, these preliminary findings suggest oxidative stress may have a role in appendicolith formation. Further research is needed to determine how dietary factors such as omega-6 fatty acids and food additives, redox-active metals and the intestinal microbiome interact with genetic factors to predispose to appendicolith formation., (© 2022. The Author(s).)

Recent single-cell studies of cancer in both mice and humans have identified the emergence of a myofibroblast population specifically marked by the highly restricted leucine-rich-repeat-containing protein 15 (LRRC15) 1-3 . However, the molecular signals that underlie the development of LRRC15 + cancer-associated fibroblasts (CAFs) and their direct impact on anti-tumour immunity are uncharacterized. Here in mouse models of pancreatic cancer, we provide in vivo genetic evidence that TGFβ receptor type 2 signalling in healthy dermatopontin + universal fibroblasts is essential for the development of cancer-associated LRRC15 + myofibroblasts. This axis also predominantly drives fibroblast lineage diversity in human cancers. Using newly developed Lrrc15-diphtheria toxin receptor knock-in mice to selectively deplete LRRC15 + CAFs, we show that depletion of this population markedly reduces the total tumour fibroblast content. Moreover, the CAF composition is recalibrated towards universal fibroblasts. This relieves direct suppression of tumour-infiltrating CD8 + T cells to enhance their effector function and augments tumour regression in response to anti-PDL1 immune checkpoint blockade. Collectively, these findings demonstrate that TGFβ-dependent LRRC15 + CAFs dictate the tumour-fibroblast setpoint to promote tumour growth. These cells also directly suppress CD8 + T cell function and limit responsiveness to checkpoint blockade. Development of treatments that restore the homeostatic fibroblast setpoint by reducing the population of pro-disease LRRC15 + myofibroblasts may improve patient survival and response to immunotherapy., (© 2022. The Author(s).)

Multiphoton microscopy has been a powerful tool in brain research, three-photon fluorescence microscopy is increasingly becoming an emerging technique for neurological research of the cortex in depth. Nonhuman primates play important roles in the study of brain science because of their neural and vascular similarity to humans. However, there are few research results of three-photon fluorescence microscopy on the brain of nonhuman primates due to the lack of optimized imaging systems and excellent fluorescent probes. Here we introduced a bright aggregation-induced emission (AIE) probe with excellent three-photon fluorescence efficiency as well as facile synthesis process and we validated its biocompatibility in the macaque monkey. We achieved a large-depth vascular imaging of approximately 1 mm in the cerebral cortex of macaque monkey with our lab-modified three-photon fluorescence microscopy system and the AIE probe. Functional measurement of blood velocity in deep cortex capillaries was also performed. Furthermore, the comparison of cortical deep vascular structure parameters across species was presented on the monkey and mouse cortex. This work is the first in vivo three-photon fluorescence microscopic imaging research on the macaque monkey cortex reaching the imaging depth of ∼1 mm with the bright AIE probe. The results demonstrate the potential of three-photon microscopy as primate-compatible method for imaging fine vascular networks and will advance our understanding of vascular function in normal and disease in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into 'hot' and 'cold' is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients., (© 2022. The Author(s).)

Four undescribed and five known isosteroidal alkaloids were isolated from the bulbs of Fritillaria taipaiensis and their structures were elucidated on the basis of HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses. The undescribed compounds were designated taipainines A-D. Of these, taipainine D presented a unique structure having the D/E trans (H-13α/H-17β) and E/F cis (β-axial lone pair of the N atom/H-22β) ring junctions. Possible biosynthetic pathway to taipainine D is proposed. Four compounds showed significant BChE inhibitory activities similar or better than the positive control galantamine. In addition, the preliminary structure-activity relationships (SARs) of these isosteroidal alkaloids were also investigated., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

It is difficult to study the gender wealth gap because wealth is usually measured at the household level, and men and women often live in the same household. I use person-level measures of wealth, attributing to each person the assets and debts owned in their name, to study the gender wealth gap in the United States among working age people. Using the Survey of Income and Program Participation, I find that the existence of the gender wealth gap is primarily explained by the gender income gap. However, although the gender income gap has narrowed, the gender wealth gap has widened from the mid-1990s to the mid-2010s. This widening occurred across the wealth distribution and among almost every subgroup by marital status, education, race, and age. This widening of the gender wealth gap cannot be explained by changes in socioeconomic characteristics but is consistent with the trend of increasing wealth inequality., Competing Interests: Declarations of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ultra-high Field (≥7T) functional magnetic resonance imaging (UHF-fMRI) provides opportunities to resolve fine-scale features of functional architecture such as cerebral cortical columns and layers, in vivo. While the nominal resolution of modern fMRI acquisitions may appear to be sufficient to resolve these features, several common data preprocessing steps can introduce unwanted spatial blurring, especially those that require interpolation of the data. These resolution losses can impede the detection of the fine-scale features of interest. To examine quantitatively and systematically the sources of spatial resolution losses occurring during preprocessing, we used synthetic fMRI data and real fMRI data from the human visual cortex-the spatially interdigitated human V2 "thin" and "thick" stripes. The pattern of these cortical columns lies along the cortical surface and thus can be best appreciated using surface-based fMRI analysis. We used this as a testbed for evaluating strategies that can reduce spatial blurring of fMRI data. Our results show that resolution losses can be mitigated at multiple points in preprocessing pathway. We show that unwanted blur is introduced at each step of volume transformation and surface projection, and can be ameliorated by replacing multi-step transformations with equivalent single-step transformations. Surprisingly, the simple approaches of volume upsampling and of cortical mesh refinement also helped to reduce resolution losses caused by interpolation. Volume upsampling also serves to improve motion estimation accuracy, which helps to reduce blur. Moreover, we demonstrate that the level of spatial blurring is nonuniform over the brain-knowledge which is critical for interpreting data in high-resolution fMRI studies. Importantly, our study provides recommendations for reducing unwanted blurring during preprocessing as well as methods that enable quantitative comparisons between preprocessing strategies. These findings highlight several underappreciated sources of a spatial blur. Individually, the factors that contribute to spatial blur may appear to be minor, but in combination, the cumulative effects can hinder the interpretation of fine-scale fMRI and the detectability of these fine-scale features of functional architecture., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The cerebral cortices of human and nonhuman primate brains are characterized by submillimeter functional domains. However, little is known about the connections of single functional domains. Here, in macaque monkey visual cortex, we have developed a targeted focal electrical stimulation method, coupled with functional optical imaging, to map cortical networks with submillimeter precision in vivo. We find that single functional domains are a part of highly specific and sparse intra-areal and inter-areal micro-networks. Across color-related and orientation-related functionalities, these micro-networks exhibit parallel connection patterns, suggesting a common domain-based architecture. Moreover, these micro-networks shift topographically at a submillimeter scale, suggesting that they serve as a fundamental unit for cortical information processing. Our findings establish a domain-based connectional architecture in the primate brain and present new constraints for cortical map representation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)