bluuebunny/crossref_metadata_2025 huggingface dataset:
Prone position ventilation for the relief of acute respiratory distress syndrome through improved pulmonary ventilation: Efficacy and safety
Authors: Liao Xianyong , Meng Lu , Zeng Zhongyi
Published: July 2023

Background

At present, there is a preliminary clinical consensus that prone position ventilation (PPV) is beneficial to the treatment of acute respiratory distress syndrome (ARDS), and further research on the details of treatment and patients' benefits will help to assess its effectiveness and safety.

Aim

To evaluate the timing, efficacy, and safety of different mechanical ventilation positions (MVP) in treating ARDS.

Study Design

The results of clinical trials were directly or indirectly compared by network meta‐analysis to compare the effects of different MVP. Two authors independently searched the papers published in PubMed, Embase, Cochrane Library, China Knowledge Infrastructure (CNKI), China Biomedical Discs (CBM), WanFang, and VIP database from January 2000 to August 2022. The outcome indicators were oxygenation index, mechanical ventilation time, ICU hospitalization time, in‐hospital mortality, and incidence of adverse events. Two authors independently screened the literature, evaluated the quality of the studies, and completed the data extraction. Stata 14.0 was used to conduct a network Meta‐analysis, and the intervention measures were ranked according to the surface under the cumulative ranking curve (SUCRA). Funnel plots were drawn to evaluate publication bias.

Results

According to the inclusion and exclusion criteria, 75 studies (including 6333 patient data) were finally included. According to the analysis results, PPV was the best for improving the oxygenation index. The SUCRA values of mechanical ventilation time, ICU hospitalization time, and in‐hospital mortality were ranked as PPV > lateral position ventilation (LPV) > supine position ventilation (SuPV) > semireclining position ventilation (SePV). The SUCRA values in the incidence of adverse events were ranked as LPV > PPV > SuPV > SePV. All outcome measures had good consistency and low statistical heterogeneity. Funnel plot analysis shows that papers reported within three days of mechanical ventilation time, over five days of mechanical ventilation time, and in‐hospital mortality were more likely to have publication bias.

Conclusions

PPV has the best effect on improving the oxygenation index, reducing mechanical ventilation time, shortening ICU hospitalization time, and reducing in‐hospital mortality. Early and long‐term use of PPV to improve pulmonary ventilatory function will be the key to improving patients' survival and quality of life with ARDS.

Relevance to clinical practice

PPV significantly affects patients with ARDS, which can shorten the treatment time and reduce hospital costs. During the treatment, nursing observation should be strengthened to prevent adverse events.
First study to assess the reliability of commonly used pain scales in children with disorders of gut‐brain interaction
Authors: Ginton Lee , Nurko Samuel , Di Lorenzo Carlo , Saps Miguel
Published: July 2023

Background

There are no validated measures to assess chronic abdominal pain (AP) in clinical trials of children with disorders of gut–brain interaction (DGBIs). Currently used AP measures are extrapolated from studies on adults or children with acute AP. The primary aim of the study was to assess the commonly used pain scales in children with DGBIs. The secondary aim of the study was to compare specific pain measures with the overall subjective assessment of AP well‐being in children.

Methods

A sub‐study from multicenter crossover randomized controlled trial (RCT) was conducted. Children with AP‐DGBIs completed daily diaries for 7 weeks. It included three widely used AP scales: the numeric rating scale (NRS), the visual analog scale (VAS), the Faces Pain Scale Revised (FPS‐R), and a global improvement question. Strength of correlations among scales and questions was assessed with the Pearson correlation coefficient (r).

Key Results

Thirty subjects completed the study. Children completed 4975 of 5880 (84.6%) pain and global responses. The VAS and NRS had strongest correlation among them, r = 0.893 (p < 0.001). The FPS‐R also demonstrated strong correlations with the VAS r = 0.773 (p < 0.001), NRS = 0.783 (p < 0.001). The three scales exhibited weaker but significant correlations with the global question. Strong correlations were consistent when stratified by age groups.

Conclusion

This is the first study to assess the most used AP scales in children with DGBIs. It supports the Rome IV recommendations on using the VAS and NRS scales. It also suggests that FPS‐R, that was not part of Rome IV, can also be used in RCTs. Congruent with the biopsychosocial model, there was a weaker correlation between AP measures and the global question. This suggests that the global question measures more domains than AP alone and that it should also be incorporated in DGBIs RCTs in children.
Melatonin attenuates dental pulp stem cells senescence due to vitro expansion via inhibiting MMP3
Authors: Zhang Zeying , Bao Yandong , Wei Penggong , Yan Xiaoyuan , Qiu Qiujing , Qiu Lihong
Published: July 2023

Objective

We aimed to identify the crucial genes involved in dental pulp stem cell (DPSC) senescence and evaluate the impact of melatonin on DPSC senescence.

Methods

Western blotting, SA‐β‐Gal staining and ALP staining were used to evaluate the senescence and differentiation potential of DPSCs. The optimal concentration of melatonin was determined using the CCK‐8 assay. Differentially expressed genes (DEGs) involved in DPSC senescence were obtained via bioinformatics analysis, followed by RT–qPCR. Gain‐ and loss‐of‐function studies were conducted to explore the role of MMP3 in DPSC in vitro expansion and in response to melatonin. GSEA was employed to analyse MMP3‐related pathways in cellular senescence.

Results

Treatment with 0.1 μM melatonin attenuated cellular senescence and differentiation potential suppression in DPSCs due to long‐term in vitro expansion. MMP3 was a crucial gene in senescence, as confirmed by bioinformatics analysis, RT–qPCR and Western blotting. Furthermore, gain‐ and loss‐of‐function studies revealed that MMP3 played a regulatory role in cellular senescence. Rescue assays showed that overexpression of MMP3 reversed the effect of melatonin on senescence. GSEA revealed that the MMP3‐dependent anti‐senescence effect of melatonin was associated with the IL6‐JAK‐STAT3, TNF‐α‐Signalling‐VIA‐NF‐κB, COMPLEMENT, NOTCH Signalling and PI3K‐AKT‐mTOR pathways.

Conclusion

Melatonin attenuated DPSC senescence caused by long‐term expansion by inhibiting MMP3.
Cutis marmorata telangiectatica congenita: Incidence of extracutaneous manifestations and a proposed clinical definition
Authors: Downey Camila , Metry Denise , Garzon Maria C. , Morales Luz Karem , Baselga Eulalia
Published: July 2023

Background/Objectives

Cutis marmorata telangiectatica congenita (CMTC) is a capillary malformation characterized by congenital, reticulated, well‐demarcated dark blue, red‐purple, or violaceous macules or plaques, with a coarse fixed livedo pattern. Nearly always, contiguous areas of skin atrophy and/or ulceration are present. CMTC is usually localized but may rarely be generalized. Such generalized cases may be a feature of Adams‐Oliver syndrome (AOS). The nosologic confusion surrounding the term CMTC and uncertainty about the risk of associated abnormalities hinders the appropriate workup of patients and prognostic counseling for families. We hypothesized that the risk of associated anomalies in children with localized CMTC is very low.

Methods

We performed a literature review and retrospective review of patients with CMTC to propose a more precise clinical definition and ascertain the risk of associated anomalies.

Results

We included 78 patients determined to have a diagnosis of CMTC based on consensus. The majority of patients had localized CMTC. Most patients with generalized CMTC met the criteria for the diagnosis of AOS. The associations found in patients with localized CMTC were mostly dermatological, with atrophy, ulcerations, or erosions present in 71%. Extracutaneous findings were present in 34.4% of patients and consisted mainly of extremity asymmetry (24.5%) that improved over time.

Conclusion

Our study showed a very low frequency of extracutaneous anomalies among patients with localized CTMC, ipsilateral limb discrepancy being the most common. We did not find a strong association with any other visceral anomalies that would justify routine evaluation in patients with localized CMTC.
Effectiveness of biologic therapies in children with palmoplantar plaque psoriasis: An analysis of real‐life data from the BiPe cohorts
Authors: Hanafi Bochra , Beauchet Alain , Di Lernia Vito , Lasek Audrey , Severino‐Freire Maëlla , Barbarot Sébastien , Hadj‐Rabia Smail , Phan Alice , Bursztejn Anne‐Claire , Maruani Annabel , Chaby Guillaume , Quiles‐Tsimaratos Nathalie , Phan Céline , Zitouni Jinane , Mazereeuw‐Hautier Juliette , Mahé Emmanuel ,   Groupe de Recherche sur le Psoriasis (GrPso) of the Société Française de Dermatologie (SFD), Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (GR SFDP), and Società Italiana di Dermatologia Pediatrica (S.I.Der.P.)
Published: July 2023

Background

Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts.

Methods

Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed.

Results

Children in the palmoplantar group were more likely to be male (p = .04), with an earlier age of psoriasis onset (p < .001), and more frequent nail involvement (p < .001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p = .004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p = .01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p = .01), and disease remission was less frequent (p = .05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p < .001).

Conclusions

This study demonstrated the treatment‐resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines.
Evaluation of the effect of a nurse navigation program developed for postpartum mothers on maternal health: A randomized controlled study
Authors: Öztoprak Pınar Uzunkaya , Koç Gülten , Erkaya Salim
Published: July 2023

Objective

This study aimed to determine the effects of a nurse navigation program on the capability for self‐care, quality of life, risk of anxiety and depression, and severity of the physical symptoms of postpartum mothers.

Methods

This prospective, parallel‐group, randomized controlled study included 64 primiparous pregnant women (32 women each in the intervention and control groups) at ≥36 gestational weeks admitted to the pregnancy outpatient clinic of a public hospital in Turkey. The intervention group received navigation program‐based nursing care comprising three home visits, four phone calls, and five text messages aside from the standard hospital care during delivery and the postpartum period. Meanwhile, the control group received only the standard hospital care during delivery and the postpartum period. Data were collected using a sociodemographic data form, the Self‐Care Power Scale, the Maternal Postpartum Quality of Life Instrument (MPQoL‐I), the Postpartum Specific Anxiety Scale (PSAS), the Edinburgh Postnatal Depression Scale (EPDS), and the Postpartum Physical Symptom Severity Scale.

Results

Mean scores for the capability for self‐care and quality of life were higher, while those for the risk of depression and anxiety were lower for the intervention group than the control group (p < .05).

Conclusions

Navigation program‐based care provided to primiparous mothers improved maternal health.
Kisspeptin promotes follicular development through its effects on modulation of P450 aromatase expression and steroidogenesis in sheep ovarian follicles
Authors: Venkata Ratna S. , Prasada Rao T. , Pathipati Deepa , Chaitanya Kumar T. V. , Rambabu Naik B. , Siva Kumar A. V. N.
Published: July 2023

The present study was conducted to ascertain whether the role of kisspeptin in promoting in vitro development of preantral follicles was through the regulation of P450 aromatase gene expression and steroidogenesis in sheep. Accordingly, the cumulus cells and oocytes were collected from different development stages of preantral follicles grown in vivo and cultured in vitro in TCM199B (Group I), TCM199B + KP (10 μg/mL) (Group II) and Standard medium + KP (10 μg/mL). To measure the steroid (Estradiol‐17β; E2 and Progesterone; P4) synthesis through ELISA, spent culture medium was collected separately from the same in vitro groups. E2 synthesis in the spent medium collected from all the three groups showed an increasing trend from PFs' exposed to respective culture media for 3 min to 2‐day culture stage but decreased thereafter till 6‐day culture stage. This is followed by a sharp increase in E2 concentration in the spent medium collected after in vitro maturation. However, P4 synthesis in group III followed increased pattern as the development progressed from PFs' exposed to culture medium for 3 min to in vitro maturation stage. The steroid production was observed at all stages of in vitro development in altered supplemented conditions. The steroid synthesis in the spent medium was highest in the 6 day cultured PFs' in Standard medium + KP matured in vitro for 24 h. Therefore, supplementation of kisspeptin along with other growth factors promoted steroid production in cultured preantral follicles far better than in other media.
Tracing the sedimentary response to the rifting and opening of the Meso‐Tethys Ocean
Authors: Fan Jian‐Jun , Zhang Bo‐Chuan , Niu Yaoling , Luo An‐Bo , Hao Yu‐Jie
Published: July 2023

Knowledge of the rifting and opening process of the Meso‐Tethys Ocean is important for understanding the evolution of the Tethys tectonic domain and for an in‐depth understanding of Tethys dynamics. Sedimentary rocks are faithful recorders of surface expressions of tectonic events and are thus expected to have recorded the rifting and opening of the Meso‐Tethys Ocean. This study presents petrography, sedimentology, zircon U–Pb geochronological data and Hf isotope data for the Carboniferous–Permian Shiquanhe stratigraphic succession in the Lhasa Terrane of the Tibetan Plateau. The data indicate that the 300 to 273 Ma Lagar and Angjie formations in the lower section of the Carboniferous–Permian Shiquanhe succession were deposited in the stable passive margin of northern Gondwana with sediment sources in Gondwanaland. However, the 273 to 252 Ma Xiala Formation in the upper section of the Carboniferous–Permian Shiquanhe succession was deposited in a tectonically active setting characterized by intense magmatic activity. Considering the transition from the Lagar and Angjie formations to the Xiala Formation, a significant change in depositional setting from tectonically stable to tectonically active occurred at ca 273 Ma. Similar Early–Middle Permian changes in depositional setting have also been identified in the South Qiangtang, Baoshan and Oman regions in the Tethyan tectonic domain. These widespread changes in depositional setting, together with Early–Middle Permian tectonic uplift and episodes of subsidence, as well as rift‐related magmatism in the South Qiangtang, Baoshan, Himalayan, Zagros, Oman and Turkey regions once located in northern Gondwana, constitute a complete record of continental rifting–ocean opening associated with the diachronous opening of the Meso‐Tethys Ocean during the Early–Middle Permian.
Development of a novel microneedle platform for biomarker assessment of atopic dermatitis patients
Authors: Lee Keun Ho , Kim Jung Dong , Jeong Do Hyeon , Kim Su Min , Park Chang Ook , Lee Kwang Hoon
Published: July 2023

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis, cause, and treatment have been extensively studied. The association of AD with Th2 cytokines is well known; therefore, the analysis of this association is crucial for the diagnosis and treatment of AD. This study aimed to present a new method for measuring protein biomarkers in patients with AD, before and after treatment, using minimally invasive microneedles.

Materials and methods

First, hyaluronic acid‐loaded microneedle patches (HA‐MNs) for skin sample collection were fabricated. Next, after Institutional Review Board approval, 20 patients with AD were recruited and skin samples were taken before and after treatment using four different sampling techniques: (1) tape stripping, (2) hydrocolloid patches, (3) hollow microneedles, and (4) HA‐MNs. Lastly, proteins were isolated from the collected samples, and AD‐related biomarkers were analyzed by enzyme‐linked immunosorbent assay.

Results

Proteins were successfully extracted from the skin samples collected by tape stripping, hydrocolloid patches, and HA‐MNs, except hollow microneedles. Interleukin (IL)‐4, IL‐13, and interferon‐γ were detected in the HA‐MNs only. By comparing the biomarker level correlation before and after treatment and the improvement score of the patients, we observed a significant negative correlation between IL‐4 and IL‐13 with an improvement in AD symptoms.

Conclusion

Overall, our results verified that HA‐MNs can be used to effectively analyze protein levels of biomarkers from skin metabolites of patients with AD and can be applied to monitor the treatment progress of patients with AD in a minimally invasive manner.
Evaluating emotional and social interactions in museum liminal spaces: A case study of the National Museum of the Islamic Revolution and Holy Defense of Tehran, Iran
Authors: Motamedi Shooka , Person Angela M.
Published: July 2023

Background

This study explores which architectural features of interstitial spaces improve visitors’ interactions with the overall museum space and with other visitors at the National Museum of the Islamic Revolution and Holy Defense in Tehran, Iran. Interstitial or liminal spaces are defined as “in‐between” spaces connecting primary spaces in a building that have a key role in relating humans to places.

Objectives

This study asks which geometric features can increase the socio‐emotional interactions for visitors.

Methods

To answer the question, observations of behavior and body language were made at the study site. These data were analyzed based on body language science and neuroscience literature. Five in‐between spaces connecting exhibition halls were selected, and visitor behaviors were observed and analyzed using the Observer XT software by Noldus.

Results

Results showed that certain types of passages were associated with the highest levels of emotional interaction, while others are associated with the highest levels of social interaction.

Conclusions

The results of this study align with earlier neuroscience findings regarding brain activities in relation to certain geometries. The methods used in this study can be applied by architects and designers in their predesign planning and post design evaluation processes to improve socio‐emotional interactions for visitors.
Prudential regulation and bank solvency based on flexible distributions: An example for evaluating the impact of monetary policy
Authors: Rendón Juan F. , Cortés Lina M. , Perote Javier
Published: July 2023

This paper proposes new risk measures by accurately estimating the components of solvency risk and focusing on prudential policy implementation. We use semi‐nonparametric statistics to model the stylised facts of the probability density functions, particularly the higher‐order moments of three variables: the solvency decline rate, the tier decline rate and the portfolio growth rate. The proposed measures allow the evaluation of the impact of expansionary monetary policy on the risk‐taking transmission channel and implementation of the minimum solvency ratios required by banking regulators based on the estimation of quantile risk metrics. Using a database of Colombian solvency indicators, we show that the liquidity injection measures employed in response to the COVID‐19 pandemic led to a significant increase in portfolio risk in the banking system. The proposed methodology is suitable for micro‐ and macroprudential regulation at different levels of portfolio risk aggregation.
Ocular examination findings and selected ophthalmic diagnostic tests in African green monkeys (Chlorocebus aethiops sabaeus)
Authors: Pletcher Jacklin S. , Zimmer Jennifer L. , Liu Chin‐Chi , Beierschmitt Amy , Lewin Andrew C.
Published: July 2023

Objective

To document ocular lesions and establish ophthalmic diagnostic test reference values in a colony of African green monkeys (Chlorocebus aethiops sabaeus).

Animals Studied

Fifty one geriatric (GAGM, 19–30 years old), 10 adult (AAGM, 5–9 years old) and 10 juvenile (JAGM, <2 years old) African green monkeys housed in a single Caribbean research colony.

Procedures

Ocular biomicroscopy, indirect fundoscopy, Schirmer tear test (STT), rebound tonometry (TonoVet®) and corneal fluorescein staining were performed. Mixed ANCOVA tests were performed to compare STT and IOP between groups.

Results

Common ocular lesions in GAGM included vitreal degeneration (27/51, 51/102 eyes) and cataracts (21/51, 32/102 eyes). Vitreal degeneration was also common in AAGM (8/10, 16/20 eyes) and infrequent in JAGM (3/10, 6/20 eyes). Cataracts were not present in any JAGM or AAGM. All eyes in all three groups had perilimbal corneal pigmentation and faint lace‐like anterior corneal stromal opacification. Median (range) STT values were 16.0 (18) mm/min in GAGM. Mean (SD) STT values were 14.2 (4.6) mm/min in AAGM, and 8.9 (3.4) mm/min in JAGM. Median (range) IOP values were 16.5 (27) mmHg in GAGM. Mean (SD) IOP values were 18.0 (2.8) mmHg in AAGM, and 14.1 (2.2) mmHg in JAGM. JAGM had significantly lower STT and IOP values compared to AAGM (p = .0449, .0057, respectively) and GAGM (p = .0002, .0130, respectively).

Conclusions

Spontaneous ocular lesions were common in geriatric monkeys in this research colony. IOP and STT values were lower in juvenile African green monkeys relative to adult or geriatric animals.
¿Es retirar la filosofía de las escuelas un acto de injusticia epistémica?
Authors: Eslava Edgar
Published: July 2023

La siempre latente posibilidad de ver que la filosofía abandone las escuelas se revisa en este texto a partir de las categorías de análisis propuestas por la teoría de la injusticia epistémica, según la cual las limitaciones, en términos de silenciamiento o de falta de reconocimiento, a que son sometidos algunos individuos cuando se les considera indignos como miembros de una comunidad epistémica representan una forma de acallamiento de su agencia epistémica. Esta perspectiva no solo permite considerar una nueva dimensión del asunto de la presencia de la filosofía en los planes de estudio escolares, sino también formular propuestas para que la enseñanza de la filosofía ayude a superar algunas de las injusticias que ella misma ha ayudado a invisibilizar.
Prediction of Fracture Initiation Pressure for Slotting-Directional Hydraulic Fracturing Based on the Anisotropy of Coal
Authors: Jingwei Zheng , Zhaolong Ge , Yiyu Lu , Zhe Zhou , Jing Zhou , Wenyu Fu
Published: July 2023

The precise estimation of fracture initiation pressure is crucial for the effective implementation of slotting-directional hydraulic fracturing methods in coal seams. Nonetheless, current models fail to account for the impact of the morphology of the slotted borehole and the anisotropy of coal. To address this issue, a three-dimensional model was created in this study, which simplified the slotted borehole as an elliptical medium and the coal as an orthotropic medium. Laboratory experiments were conducted to validate the model, and the findings regarding the changes in fracture initiation pressure and deflection angle due to various factors were presented. The calculated outcomes of the proposed model align with the observed pattern of the experimental results, and the numerical discrepancy falls within the acceptable range of 7%, showcasing the precision of the proposed model. A rise in the horizontal stress difference and a decrease in the depth of the slots will result in an elevation of the fracture initiation pressure and deflection angle. In addition, the slotting angle will impact the distribution pattern of the fracture initiation pressure and deflection angle, underscoring the significance of these factors in the hydraulic fracturing of slotted boreholes.
XPS characterization of cobalt nitrate
Authors: Rincón-Ortiz Sergio A. , Quintero-Orozco Jorge H. , Ospina Rogelio
Published: July 2023

X-ray photoelectron spectroscopy was used to characterize cobalt nitrate. The specimen is a powder purchased from Sigma Aldrich and was fixed to a stainless-steel sample holder with copper 3MTM double-sided adhesive tape. Survey spectra and Co 2p, N 1s, O 1s, C 1s, and Co 3p core level spectra were acquired. Results evidenced the chemical surface state and interactions of elements that constitute the cobalt nitrate.
Passive source depth estimation using beam intensity striations of a horizontal linear array in deep water
Authors: Wu Yanqun , Li Pingzheng , Guo Wei , Zhang Bingbing , Hu Zhengliang
Published: July 2023

Source depth estimation is an important yet very difficult task for passive sonars, especially for horizontal linear arrays (HLAs). This paper proposes an efficient two-step depth estimation scheme using narrowband and broadband constructive and deconstructive striation patterns due to interference between the direct (D) and sea surface reflected (SR) arrivals at an HLA on the bottom of deep water. First, the horizontal source-array ranges are derived from triangulation results of solid angle estimates by subarray beamforming. The applicable areas of the method in deep water are investigated through Mento Carlo simulations, assuming different subarray partitioning ways of a given HLA aperture. Second, cost functions are built to match the measured beam intensity striations with modeled ones. To mitigate the spatial smoothing effect of the beam intensity striations during beamforming, a criterion of the largest subarray aperture is established, and a computationally efficient way is presented to model the replicas by the D-SR time delay templates at a single element of the array calculated by ray theory. The performance degradation due to limited source range spans, the distortion of the beam intensity striations, and range estimation errors has been analyzed. Two experimental datasets verify the effectiveness of the proposed method.
Telecom-band–integrated multimode photonic quantum memory
Authors: Zhang Xueying , Zhang Bin , Wei Shihai , Li Hao , Liao Jinyu , Li Cheng , Deng Guangwei , Wang You , Song Haizhi , You Lixing , Jing Bo , Chen Feng , Guo Guangcan , Zhou Qiang
Published: July 2023

Telecom-band–integrated quantum memory is an elementary building block for developing quantum networks compatible with fiber communication infrastructures. Toward such a network with large capacity, an integrated multimode photonic quantum memory at telecom band has yet been demonstrated. Here, we report a fiber-integrated multimode quantum storage of single photon at telecom band on a laser-written chip. The storage device is a fiber-pigtailed Er
3+
:LiNbO
3
waveguide and allows a storage of up to 330 temporal modes of heralded single photon with 4-GHz-wide bandwidth at 1532 nm and a 167-fold increasing of coincidence detection rate with respect to single mode. Our memory system with all-fiber addressing is performed using telecom-band fiber-integrated and on-chip components. The results represent an important step for the future quantum networks using integrated photonics devices.
RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome–associated cardiac hypertrophy
Authors: Cuevas-Navarro Antonio , Wagner Morgan , Van Richard , Swain Monalisa , Mo Stephanie , Columbus John , Allison Madeline R. , Cheng Alice , Messing Simon , Turbyville Thomas J. , Simanshu Dhirendra K. , Sale Matthew J. , McCormick Frank , Stephen Andrew G. , Castel Pau
Published: July 2023

RIT1 is a RAS guanosine triphosphatase (GTPase) that regulates different aspects of signal transduction and is mutated in lung cancer, leukemia, and in the germline of individuals with Noonan syndrome. Pathogenic RIT1 proteins promote mitogen-activated protein kinase (MAPK) hyperactivation; however, this mechanism remains poorly understood. Here, we show that RAF kinases are direct effectors of membrane-bound mutant RIT1 necessary for MAPK activation. We identify critical residues in RIT1 that facilitate interaction with membrane lipids and show that these are necessary for association with RAF kinases and MAPK activation. Although mutant RIT1 binds to RAF kinases directly, it fails to activate MAPK signaling in the absence of classical RAS proteins. Consistent with aberrant RAF/MAPK activation as a driver of disease, we show that pathway inhibition alleviates cardiac hypertrophy in a mouse model of
RIT1
mutant Noonan syndrome. These data shed light on the function of pathogenic RIT1 and identify avenues for therapeutic intervention.
Glyoxal fixation: An approach to solve immunohistochemical problem in neuroscience research
Authors: Konno Kohtarou , Yamasaki Miwako , Miyazaki Taisuke , Watanabe Masahiko
Published: July 2023

The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to target molecules that are buried within specialized neuronal components, such as ionotropic receptors at the postsynapse and voltage-gated ion channels at the axon initial segment, often requiring additional antigen-exposing techniques to detect their authentic signals. To solve this problem, we used glyoxal, a two-carbon atom di-aldehyde. We found that glyoxal fixation greatly improved antibody penetration and immunoreactivity, uncovering signals for buried molecules by conventional immunohistochemical procedures at light and electron microscopic levels. It also enhanced immunosignals of most other molecules, which are known to be detectable in formaldehyde-fixed sections. Furthermore, we unearthed several specific primary antibodies that were once judged to be unusable in formaldehyde-fixed tissues, allowing us to successfully localize so far controversial synaptic adhesion molecule Neuroligin 1. Thus, glyoxal is a highly effective fixative for immunostaining, and a side-by-side comparison of glyoxal and formaldehyde fixation is recommended for routine immunostaining in neuroscience research.
Genome-wide CRISPR screens define determinants of epithelial-mesenchymal transition mediated immune evasion by pancreatic cancer cells
Authors: Gu Yuanzhuo , Zhang Zhengkui , Camps Marcel G. M. , Ossendorp Ferry , Wijdeven Ruud H. , ten Dijke Peter
Published: July 2023

The genetic circuits that allow cancer cells to evade immune killing via epithelial mesenchymal plasticity remain poorly understood. Here, we showed that mesenchymal-like (Mes) KPC3 pancreatic cancer cells were more resistant to cytotoxic T lymphocyte (CTL)–mediated killing than the parental epithelial–like (Epi) cells and used parallel genome-wide CRISPR screens to assess the molecular underpinnings of this difference. Core CTL-evasion genes (such as IFN-γ pathway components) were clearly evident in both types. Moreover, we identified and validated multiple Mes-specific regulators of cytotoxicity, such as Egfr and Mfge8. Both genes were significantly higher expressed in Mes cancer cells, and their depletion sensitized Mes cancer cells to CTL-mediated killing. Notably, Mes cancer cells secreted more Mfge8 to inhibit proliferation of CD8
+
T cells and production of IFN-γ and TNFα. Clinically, increased Egfr and Mfge8 expression was correlated with a worse prognosis. Thus, Mes cancer cells use Egfr-mediated intrinsic and Mfge8-mediated extrinsic mechanisms to facilitate immune escape from CD8
+
T cells.
Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease restoring striatal synaptic plasticity
Authors: Marino Gioia , Campanelli Federica , Natale Giuseppina , De Carluccio Maria , Servillo Federica , Ferrari Elena , Gardoni Fabrizio , Caristo Maria Emiliana , Picconi Barbara , Cardinale Antonella , Loffredo Vittorio , Crupi Francesco , De Leonibus Elvira , Viscomi Maria Teresa , Ghiglieri Veronica , Calabresi Paolo
Published: July 2023

Intensive physical activity improves motor functions in patients with Parkinson’s disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of
N
-methyl-
d
-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas.
A three-stage developmental pathway for human Vγ9Vδ2 T cells within the postnatal thymus
Authors: Perriman Louis , Tavakolinia Naeimeh , Jalali Sedigheh , Li Shuo , Hickey Peter F. , Amann-Zalcenstein Daniela , Ho William Wing Ho , Baldwin Tracey M. , Piers Adam T. , Konstantinov Igor E. , Anderson Jeremy , Stanley Edouard G. , Licciardi Paul V. , Kannourakis George , Naik Shalin H. , Koay Hui-Fern , Mackay Laura K. , Berzins Stuart P. , Pellicci Daniel G.
Published: July 2023

Vγ9Vδ2 T cells are the largest population of γδ T cells in adults and can play important roles in providing effective immunity against cancer and infection. Many studies have suggested that peripheral Vγ9Vδ2 T cells are derived from the fetal liver and thymus and that the postnatal thymus plays little role in the development of these cells. More recent evidence suggested that these cells may also develop postnatally in the thymus. Here, we used high-dimensional flow cytometry, transcriptomic analysis, functional assays, and precursor-product experiments to define the development pathway of Vγ9Vδ2 T cells in the postnatal thymus. We identify three distinct stages of development for Vγ9Vδ2 T cells in the postnatal thymus that are defined by the progressive acquisition of functional potential and major changes in the expression of transcription factors, chemokines, and other surface markers. Furthermore, our analysis of donor-matched thymus and blood revealed that the molecular requirements for the development of functional Vγ9Vδ2 T cells are delivered predominantly by the postnatal thymus and not in the periphery. Tbet and Eomes, which are required for IFN-γ and TNFα expression, are up-regulated as Vγ9Vδ2 T cells mature in the thymus, and mature thymic Vγ9Vδ2 T cells rapidly express high levels of these cytokines after stimulation. Similarly, the postnatal thymus programs Vγ9Vδ2 T cells to express the cytolytic molecules, perforin, granzyme A, and granzyme K. This study provides a greater understanding of how Vγ9Vδ2 T cells develop in humans and may lead to opportunities to manipulate these cells to treat human diseases.
Gluten induces rapid reprogramming of natural memory αβ and γδ intraepithelial T cells to induce cytotoxicity in celiac disease
Authors: Kornberg Adam , Botella Theo , Moon Christine S. , Rao Samhita , Gelbs Jared , Cheng Liang , Miller Jonathan , Bacarella Alyssa M. , García-Vilas Javier A. , Vargas Justin , Yu Xuechen , Krupska Izabela , Bush Erin , Garcia-Carrasquillo Reuben , Lebwohl Benjamin , Krishnareddy Suneeta , Lewis Suzanne , Green Peter H. R. , Bhagat Govind , Yan Kelley S. , Han Arnold
Published: July 2023

Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4
+
T cell activation culminates in intraepithelial T cell (T-IEL)–mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4
+
follicular T helper (T
FH
) cells, regulatory T cells (T
regs
), and natural CD8
+
αβ and γδ T-IELs. Natural CD8
+
αβ and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αβ and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4
+
T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4
+
T cells after gluten ingestion.
The Mar, Sox, and Rob Systems
Authors: Chubiz Lon M.
Published: July 2023

Environments inhabited by
Enterobacteriaceae
are diverse and often stressful. This is particularly true for
Escherichia coli
and
Salmonella
during host association in the gastrointestinal systems of animals.
Pachyvitelliform maculopathy: an optical coherence tomography analysis of a novel entity
Authors: Hilely Assaf , Au Adrian , Lee Won Ki , Fogel Levin Miri , Zur Dinah , Romero-Morales Veronica , Santina Ahmad , Lee Jong Suk , Loewenstein Anat , Sarraf David
Published: July 2023

Purpose

To describe the optical coherence tomography features of pachyvitelliform maculopathy (PVM), an acquired vitelliform lesion (AVL) associated with pachychoroid disease.

Methods

This study was a retrospective, multicentre, observational analysis.

Medical records and multimodal imaging were reviewed in all patients with pachychoroid disease and AVL. Visual acuity, central choroidal thickness (CCT), AVL dimensions, total choroidal area, luminal choroidal area, stromal choroidal area and choroidal vascular index were measured in all eyes with PVM and compared with normal age-matched control eyes.

Results

Mean age of the PVM group (17 eyes of 17 patients) was 71.41 years. Average follow-up was 33.15 months. Baseline VA was 20/40 in the PVM group and declined to 20/100 (p=0.006). AVLs were all detected overlying pachyvessels with optical coherence tomography and were all hyperautofluorescent with fundus autofluorescent imaging. Mean CCT in the PVM group was significantly greater (352.35 µm) than the CCT in the control group (226.88 µm, p<0.001). Retinal pigment epithelium (RPE) disruption was present in 64.71% of eyes with PVM at baseline and 41.18% developed macular atrophy at the end of follow-up.

Conclusions

PVM, defined by the presence of AVL associated with pachychoroid features, is a distinct novel entity of the pachychoroid disease spectrum. This study suggests a possible pathogenesis of RPE dysfunction secondary to a thick choroid, leading to accumulation of undigested photoreceptor outer segments and AVL. Clinicians should be aware of this common cause of vitelliform lesions and the poor visual prognosis due to the high risk of atrophy development.
Making research ethics work for global health: towards a more agile and collaborative approach
Authors: Chattopadhyay Sreeparna , de Kok Bregje
Published: July 2023

In this reflective essay, we seek to engage in a constructive dialogue with scholars across medicine, public health and anthropology on research ethics practices. Drawing on anthropological research and ethical dilemmas that our colleagues and we encountered as medical anthropologists, we reflect on presumed and institutionalised ‘best’ practices such as mandatory written informed consent, and problematise how they are implemented in interdisciplinary global health research projects. We demonstrate that mandatory, individualised, written, informed consent may be unsuitable in many contexts and also identify reasons why tensions between professionals in interdisciplinary teams may arise when decisions about ethics procedures are taken. We propose alternatives to written informed consent that acknowledge research governance requirements and contextual realities and leave more room for ethnographic approaches. Beyond informed consent, we also explore the situatedness of ethical practices when working in contexts where decision-making around health is clearly a shared concern. We use vignettes based on our own and colleagues’ experiences to illustrate our arguments, using the collective ‘we’ instead of ‘I’ in our vignettes to protect our research participants, partners and interlocutors. We propose a decolonial, plural and vernacular approach to informed consent specifically, and research ethics more broadly. We contend that ethics procedures and frameworks need to become more agile, decolonial, pluralised and vernacularised to enable achieving congruence between communities’ ideas of social justice and institutional ethics. We argue that global health research can benefit from anthropology’s engagement with situated ethics and consent that is relational, negotiated and processual; and accountability that is not only bureaucratic but also constructive. In doing so, we hope to broaden ethical praxis so that the best outcomes that are also just, fair and equitable can be achieved for all stakeholders.
Need for a nutrition-specific scientific paradigm for research quality improvement
Authors: Flanagan Alan , Bradfield James , Kohlmeier Martin , Ray Sumantra
Published: July 2023

Nutrition science has been criticised for its methodology, apparently contradictory findings and generating controversy rather than consensus. However, while certain critiques of the field are valid and informative for developing a more cogent science, there are also unique considerations for the study of diet and nutrition that are either overlooked or omitted in these discourses. The ongoing critical discourse on the utility of nutrition sciences occurs at a time when the burden of non-communicable cardiometabolic disease continues to rise in the population. Nutrition science, along with other disciplinary fields, is tasked with producing a translational evidence-base fit for the purpose of improving population and individual health and reducing disease risk. Thus, an exploration of the unique methodological and epistemic considerations for nutrition research is important for nutrition researchers, students and practitioners, to further develop an improved scientific discipline for nutrition. This paper will expand on some of the challenges facing nutrition research, discussing methodological facets of nutritional epidemiology, randomised controlled trials and meta-analysis, and how these considerations may be applied to improve research methodology. A pragmatic research paradigm for nutrition science is also proposed, which places methodology at its centre, allowing for questions over both how we obtain knowledge and research design as the method to produce that knowledge to be connected, providing the field of nutrition research with a framework within which to capture the full complexity of nutrition and diet.
Saturday Pap Smear Clinic: addressing barriers to cervical cancer screening
Authors: Strelow Brittany , Francis Mollie , Gertner Gabrielle , Olson Rachel , Abuhadid Kholood , Abdi Deqa , Anderson Jordan , Fellows Nicole , Fink Stephanie , Stevens Joy , Peters Sonya , Stolp Anne , Tweedy Johanna , O'Laughlin Danielle
Published: July 2023

Background

The incidence of cervical cancer has decreased by 70% since the 1950s. Preventative measures include vaccination against HPV strains and Papanicolaou tests. Early identification of cervical cancer through routine screening can significantly improve patient outcomes.

Materials and methods

At our academic institution, Community Internal Medicine (CIM) Clinic, 63% of female patients aged 21–65 were compliant with cervical cancer screening. The opening of the ‘Saturday Pap Smear Clinic’ sought to address barriers by offering non-traditional appointment times on Saturday mornings with an all female staff. Our aim was to increase the cervical cancer screening rate by 1% within 12 weeks. Our team compared CIM (intervention) and family medicine (FM) (control) compliance rates from September 2021 to January 2022. Messages were sent to the patient indicating non-compliance and offering options to complete screening.

Results

At the start of this study, 5239 CIM patients were cervical cancer screening non-compliant. Postintervention, cervical screening rates among non-compliant women within CIM improved by 1.2%. The intervention cohort, CIM patients, had a significant improvement in compliance compared with the control group, FM patients. White women between the ages of 50 and 65 comprised the majority of patients who used the ‘Saturday Pap Smear Clinic’.

Conclusions

The availability of Saturday appointments for cervical cancer screening completion can enhance cervical cancer screening compliance among eligible women. Eliminating barriers for women can improve health outcomes.