bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of lung carcinoma with a unique biphasic feature: Implications for histogenesis of “fake mucoepidermoid carcinoma” developing in the peripheral lung
Authors: Kumagai Eita , Matsumura Mai , Kato Ikuma , Arai Hiromasa , Suzuki Takehisa , Sugiyama Misaki , Sekiya Motoki , Mitsui Hideaki , Kataoka Toshiaki , Iwashita Hiromichi , Okudela Koji
Published: August 2023

We present a case of lung carcinoma with a unique biphasic feature. The patient was a 67‐year‐old male smoker with idiopathic pulmonary fibrosis (IPF). A subpleural tumor in the left lower lobe, embedded in fibrotic tissue, was resected. Histologically, the tumor consisted of major and minor components of mucoepidermoid carcinoma (MEC) and surrounding conventional lepidic adenocarcinoma, respectively. Both components had the same TP53 somatic mutation (p.V157F) but not Mastermind‐like 2 (MAML2) gene rearrangement. The two components may have developed from an identical origin. The tumor could be trans‐differentiating from lepidic adenocarcinoma to MEC, possibly promoted by IPF‐induced tissue damage. The final diagnosis was “adenosquamous carcinoma with mucoepidermoid‐like features (that may originate from lepidic adenocarcinoma).” This case has implications for the potential histogenesis of peripheral lung MEC. Over time, the MEC would expand and outgrow the lepidic adenocarcinoma, making it impossible to distinguish between fake and true MEC. The present case suggests that peripheral MEC could differ from proximal MEC in its histogenesis and molecular genetics. Thus, careful examination is necessary to diagnose peripheral lung MEC, particularly in patients with interstitial lung diseases.
National security in presidential time: The politics of the National Security Council
Authors: Snyder Neil
Published: August 2023

The National Security Council (NSC) is the preeminent national security feature of the modern U.S. presidency. The NSC is the president's council, but presidents have varied dramatically in how frequently they have convened formal meetings of the NSC since the NSC system was created in 1947. Under what conditions are presidents likely to hold NSC meetings? I argue that presidents are pragmatic about when to engage personally in national security affairs and that presidents are incentivized to conduct NSC meetings more frequently early in a presidency. Using a novel data set of all NSC meetings from 1947 to 1993, I find that presidents are likely to hold NSC meetings most frequently in the first year of office and that NSC meeting frequency is likely to decline substantially over a president's first 3 years in office, even after controlling for important international security conditions and domestic political factors previously thought to influence presidential national security behavior. The results affirm prior scholars' description of the NSC as a presidential mechanism for international crisis management but also suggest that time in office is an important determinant of presidential national security behavior.
Interoception and the musical brain: Evidence from cross‐sectional and longitudinal behavioral and resting‐state fMRI study
Authors: Herman Aleksandra M. , Olszewska Alicja , Gaca Maciej , Droździel Dawid , Marchewka Artur
Published: August 2023

Musical training has been linked to enhanced interoceptive abilities and increased resting‐state (RS) functional connectivity (FC) within the interoceptive brain network. We aimed to replicate and extend these findings with a unique cross‐sectional and longitudinal study design. Professional musicians and matched individuals with no prior musical experience (training group) were recruited. Participants underwent RS fMRI scans and completed heartbeat counting and discrimination tasks outside of the scanner (time point 1). The training group additionally had RS scans and interoception tests repeated after a 6‐month‐long keyboard course training (time point 2). We found no evidence for increased interoceptive abilities in professional musicians relative to non‐musicians, nor did we observe any improvements in interoception over the course of musical training. RS FC analysis revealed increased FC within the sensorimotor network in professional musicians compared to the training group at the first time point with no change in FC over time in the Training group. These findings challenge the view that musical training may improve interoceptive abilities. Yet, the results suggest that musical training is related to increased communication within the sensorimotor RS network, which consists of some hubs important for interoceptive processing (namely pre‐ and postcentral gyri and supplementary motor area).
Neural mechanisms for integrating time and visual velocity cues in a prediction motion task: An fNIRS study
Authors: Qin Kuiyuan , Liu Yu , Liu Saifang , Li Ying , Li Yuan , You Xuqun
Published: August 2023

Human beings use accurate estimates of the time‐to‐collision of moving objects effortlessly in everyday life. In the laboratory, researchers typically apply prediction motion (PM) tasks to investigate motion processing. In the PM tasks, time structure refers to the ratio of travel time between the visible segment (first segment) and occluded segment (second segment). The condition of T = 1.0, which indicates that the time spent moving is the same across the two segments, is called equal time structure. The present study investigated the neural mechanisms of time and visual velocity information in prediction motion using functional near‐infrared spectroscopy (fNIRS). Experiment 1 showed that when visual velocity was not available, participants performed better in equal time structure conditions than in unequal time structure conditions. Moreover, the left inferior parietal lobe (IPL) showed higher activation under equal time structure conditions. Experiment 2 showed that participants also performed better in equal time structure conditions when visual velocity was available. Both the left IPL and superior parietal lobe (SPL) exhibited stronger activation under equal time structure conditions in Experiment 2. A comparison between the two experiments showed that participants integrated time structure and visual velocity to estimate arrival time of the moving object. The fNIRS data indicated that the left SPL could be involved in information integration when judging arrival time.
Rethinking complementarity: The co‐evolution of public and private governance in corporate climate disclosure
Authors: Elliott Christian , Janzwood Amy , Bernstein Steven , Hoffmann Matthew
Published: August 2023

In its 20 years of operation, the Carbon Disclosure Project (CDP) has been enormously successful as a private governor of corporate climate risk disclosure. Despite an influx of potentially competitive government‐led disclosure initiatives and interventions, the use of CDP's platform has nonetheless accelerated. To explain this outcome, we argue that public interventions augment the value of private governance for firms when the costs of compliance overlap, benefits of compliance with private rules are undiminished, and normalization helps kickstart positive feedback effects. These conditions of complementarity are made possible by private governors leveraging authority, access, and adaptability as public responses materialize. We illustrate our argument with two cases: the Non‐Financial Reporting Directive in the European Union and the G20's Task Force for Climate‐Related Financial Disclosures. In elaborating the conditions for complementarity beyond a functional division of governing labor, our study helps clarify how public and private governance co‐evolve in a mutually reinforcing manner.
Estimation of fine sediment stocks in gravel bed rivers including the sand fraction
Authors: Deng Junjian , Camenen Benoît , Legout Cédric , Nord Guillaume
Published: August 2023

Fine sediment stored in the gravel bed is an important component of river systems. Current field protocols usually allow evaluation of the silt–clay fraction of fine sediment stocks only and neglect the sand fraction. This study proposes a new protocol to quantify fine sediment stocks, including the sand fraction inside the gravel bed matrix. Fine sediment stocks were sampled within patches of 0.30 m × 0.30 m on the dry gravel bed surface, separating the surface layer and the subsurface layer. The grain‐size distribution of the samples was obtained by field sieving (10 mm, 2 mm, 500 μm and 100 μm) over a bucket, using a known volume of water. The mass of the fraction below 100 μm was measured based on the concentration within the bucket. The local stocks were then integrated over the whole river reach by assigning local stocks to facies, in which fine sediment stocks were assumed to be homogeneously distributed. The methodology was applied to a 1 km long reach of the River Galabre (Southern French Alps), characterized by significant fine sediment stocks and upstream sediment input. Results from local measurements show a large amount of sand in both surface and subsurface layers. The quantity of sand can reach up to three times the quantity of silt–clay. An estimation of porosity showed that fine material may play an important role in structuring the bed, since porosity increases with increasing fine sediment content. The potential fine sediment stock that can be resuspended due to channel migration is found to be of the same order of magnitude as the sediment budget estimated from the measured flux in the upstream hydrometric station of the studied reach.
Relapsing/remitting multiple sclerosis: A speculative model and its implications for a novel treatment
Authors: Bretscher Peter
Published: August 2023

The clinical pattern in relapsing/remitting multiple sclerosis may be accounted for if an autoreactive immune response can transition back and forth between inflammatory, pathogenic, and non‐inflammatory, non‐pathogenic modes. Such ‘back‐and‐forth’ immune responses are rare. I speculate how such back‐and‐forth immune responses may arise. Understanding the nature of these different modes, and what controls their mutual transition, may help in designing strategies to favour the nonpathogenic mode, thus constituting treatment. Antigen dose is known to be critical in determining the class/subclass of primary immune responses. Observations have led us to suggest the level of antigen also similarly influences the class/subclass of on‐going immune responses. I propose the relapsing, inflammatory and the remitting modes are respectively sustained by relatively low and high amounts of the responsible autoantigens, as is the case, for example, for Th1 and Th2 responses to foreign antigens. In addition, I propose more self‐antigens are released during an inflammatory than during a remitting mode. The decrease in the amount of antigen released, as the response transitions from an inflammatory to a remitting mode, results in time in a decreased level of antigen and so the response again evolves towards the inflammatory mode. The inflammatory mode then leads to an increased release of antigen and so, in time, to remission. This model thus explains the transition between different modes. I outline non‐invasive, testable predictions of the hypothesis. If confirmed, it may be ethical to examine whether the non‐inflammatory mode can be sustained by administering myelin antigens during the remitting phase.
A gender story of institutional disengagement of young adults in Latin America
Authors: Liu Chia , Castro Torres Andrés Felipe , Batyra Ewa
Published: August 2023

Latin America is home to many young adults who are neither engaged in formal education nor work, controversially dubbed as “nini” (“ni” trabajan “ni” estudian, denoting neither working nor studying). At the same time, early union formation and parenthood are pervasive in the region. Theories pertaining to the linkage between parenthood and female labor force participation are heavily based on evidence found in the Global North, with limited research on the topic in settings with less stable family structures, such as Latin American countries. This study tests the role household structure and family formation play on institutional disengagement of young adults in 12 Latin American countries. We explore the gender dynamic of human capital stagnation by focusing on early parenthood and conjugal partnership for women and men aged 20–25. We use censuses from the Integrated Public‐Use Microdata Series and country‐specific linear regression models. Our results reveal that the intersection of class and gender is a major determinant of institutional disengagement in the region. Women from lower social origins who leave parental home to enter conjugal union and parenthood at younger ages are particularly at risk. This study highlights the urgency of contextualizing the interplay between work and family within the framework of regional family norms, prompting further dialogues concerning the social implications of perceived inactivity.
Genomic full‐length sequence of the HLA‐B*13:64 allele was identified in a Chinese bone marrow donor
Authors: Han Bin , Feng Zhi‐Hui , Chi Xiao‐Yun , Jiao Shu‐Xian , Pang Shu‐Tao
Published: August 2023

Genomic full‐length sequence of HLA‐B*13:64 was identified in a Chinese individual by sequence‐based typing.
A review of the tectonic, volcanological and hazard history of Vulcano (Aeolian Islands, Italy)
Authors: De Astis Gianfilippo , Doronzo Domenico M. , Di Vito Mauro A.
Published: August 2023

Vulcano is one of the seven volcanic islands composing the Aeolian Islands archipelago (Southern Italy), which also includes three other active volcanoes. The island was originally a stratovolcano like Stromboli; afterwards, its shape turned towards a complex structure composed of several volcanic landforms of different sizes. This is due to the great variability of the tectonic and volcanic phenomena, presently showing a volcano made by two calderas, a lava dome complex and two small active cones. The largest of them is the tuff cone of La Fossa, hosted in the middle of a 3‐km‐wide caldera structure (La Fossa caldera), whose borders are visible on the southern and western sides of the island. Its last eruption occurred in 1888–1890. At present, Vulcano is characterized by weak shallow seismicity and intense fumarolic activity mainly concentrated within the crater of the La Fossa cone and along its rims during a recent unrest phase started in 2021, and measured with a multiparametric monitoring network.
Higher pro‐inflammatory cytokines IL‐6 and IFN‐γ are associated with anti‐SARS‐CoV‐2 spike protein‐specific seroconversion in renal allograft recipients
Authors: Yadav Brijesh , Prasad Narayan , Kushwaha Ravi Shankar , Patel Manas Ranjan , Bhadauria Dharmendra , Kaul Anupma
Published: August 2023

Background

Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS‐CoV‐2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune‐related complications.

Methods

RTRs, either acquired SARS‐CoV‐2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS‐CoV‐2, were recruited in the study. Thirty‐five unvaccinated RTRs, without anti‐SARS‐CoV‐2 spike protein‐specific antibodies, were also included as control. Cytokines interleukine‐6 (IL‐6), interferon‐γ (IFN‐γ), TGF‐β, and IL‐10 were measured using ELISA. The SARS‐CoV‐2 spike protein‐specific IgG‐titer was measured by chemiluminescent microparticle immunoassay methods.

Results

The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45–1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52–3838.75). The IL‐6, IFN‐γ, TGF‐β, and IL‐10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro‐inflammatory cytokines IL‐6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN‐γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non‐seroconverter. Similarly, in the vaccination group, pro‐inflammatory cytokines IL‐6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN‐γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non‐seroconverter. In contrast, TGF‐β (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non‐seroconverter.

Conclusions

Pro‐inflammatory cytokines IL‐6 and IFN‐γ were significantly associated with seroconversion after SARS‐CoV‐2 infection and vaccination in RTRs.

image
Community‐level incidence and treatment seeking during febrile illness: Insights from health behaviour surveys in rural Thailand and Laos
Authors: Haenssgen Marco J. , Charoenboon Nutcha , Early Annabelle , Althaus Thomas
Published: August 2023

Objective

Critical gaps remain in understanding community perceptions and treatment‐seeking behaviours in case of fever. This is especially relevant considering global antimicrobial resistance, where fever is assumed to provoke non‐judicious antibiotic use. Our study objective was therefore to document the community‐level incidence of fever, the resulting treatment‐seeking processes, and their underlying behavioural drivers.

Methods

In a cross‐sectional observational design, we used descriptive and inferential statistics and multivariable regression analysis to estimate the population‐level incidence of fever and individual and socio‐economic factors associated with treatment‐seeking process characteristics. We utilised a detailed publicly available survey of community‐level treatment‐seeking behaviour (collected in 2017/2018), comprising a representative sample of 2130 rural adults in Thailand (Chiang Rai Province) and Lao PDR (Salavan Province).

Results

Fever was reported by 7.1% of the rural adult population in Chiang Rai (95% CI: 5.1%–9.0%) and 7.5% in Salavan (95% CI: 4.5%–10.5%) during a 2‐month recall period. Treatment‐seeking patterns varied by socio‐economic characteristics like precarious employment. 69.3% (95% CI: 60.8%–77.7%) of fever episodes involved access to formal (public/private) healthcare providers, 11.0% (95% CI: 4.5%–17.5%) involved informal providers, and 24.3% (95% CI: 16.6%–32.1%) took place without either formal or informal healthcare access. Febrile patients had on average 0.39 antibiotic use episodes when accessing formal healthcare settings, compared to 0.05 otherwise (p < 0.01).

Conclusion

Treatment‐seeking behaviour during fever varies according to population characteristics. Clinical studies would benefit from contextualising quantitative outcomes. Treatment algorithms for non‐malarial febrile illnesses should involve outreach to informal healthcare and community settings to support patients in precarious circumstances, and antibiotic resistance interventions should prioritise formal healthcare facilities.
Comparison of equine paranasal sinus trephination complications and outcome following standing computed tomography, radiography and sinoscopy guided approaches for the treatment of sinusitis
Authors: Hopfgartner Teresa , Brown James A. , Adams M. Norris , Werre Stephen R.
Published: August 2023

Objective

The recent availability of standing computed tomography (CT) for equine paranasal sinus disease has enhanced diagnosis and enabled more targeted surgery compared to radiography and sinoscopy. To date, there have been no studies which have critically evaluated the benefit of preoperative CT versus radiography and sinoscopy on complications and outcome in horses undergoing sinus trephination.

Study design

Retrospective study.

Animals

A total of 229 equids.

Methods

The medical records of equids (229) presented for sinusitis treated via trephination that had CT, radiography and/or sinoscopy at time of surgery between 2009 and 2022 were reviewed. Outcome and complications were evaluated for six different pre‐ and intraoperative imaging modalities.

Results

The six groups did not differ in demographics or disease category, though equids with less weight (p = .0179) and shorter disease duration (p = .0075) were more likely to have radiography and sinoscopy based surgical planning. Short‐term postoperative complications occurred in 30.1% and were higher in groups using preoperative CT imaging (p = .01), with hemorrhage being the most common surgical complication. Following initial trephination surgery, 57.0% (127/223) of cases resolved and there was no difference between the imaging groups. Final resolution after follow‐up medical or surgical treatment increased to 94.6% (211/223) and was not different between the imaging groups or between primary or secondary sinusitis. Additional nasal fenestrations to improve sinonasal drainage, maxillary septal bulla fenestrations and trephinations to treat nasal conchal bullae were made in the CT groups.

Clinical significance

CT provided additional diagnostic information and enabled different surgical approaches but did not improve resolution in this study population.
Schurian‐finiteness of blocks of type A$A$ Hecke algebras
Authors: Ariki Susumu , Lyle Sinéad , Speyer Liron
Published: August 2023

For any algebra over an algebraically closed field , we say that an ‐module is Schurian if . We say that is Schurian‐finite if there are only finitely many isomorphism classes of Schurian ‐modules, and Schurian‐infinite otherwise. By work of Demonet, Iyama and Jasso, it is known that Schurian‐finiteness is equivalent to ‐tilting‐finiteness, so that we may draw on a wealth of known results in the subject. We prove that for the type Hecke algebras with quantum characteristic , all blocks of weight at least 2 are Schurian‐infinite in any characteristic. Weight 0 and 1 blocks are known by results of Erdmann and Nakano to be representation finite, and are therefore Schurian‐finite. This means that blocks of type Hecke algebras (when ) are Schurian‐infinite if and only if they have wild representation type if and only if the module category has finitely many wide subcategories. Along the way, we also prove a graded version of the Scopes equivalence, which is likely to be of independent interest.
A phospho‐deficient α3 glycine receptor mutation alters synaptic glycine and GABA release in mouse spinal dorsal horn neurons
Authors: Werynska Karolina , Neumann Elena , Cramer Teresa , Ganley Robert P. , Gingras Jacinthe , Zeilhofer Hanns Ulrich
Published: August 2023

Glycine receptors (GlyRs), together with GABAA receptors, mediate postsynaptic inhibition in most spinal cord and hindbrain neurons. In several CNS regions, GlyRs are also expressed in presynaptic terminals. Here, we analysed the effects of a phospho‐deficient mutation (S346A) in GlyR α3 subunits on inhibitory synaptic transmission in superficial spinal dorsal horn neurons, where this subunit is abundantly expressed. Unexpectedly, we found that not only were the amplitudes of evoked glycinergic inhibitory postsynaptic currents (IPSCs) significantly larger in GlyRα3(S346A) mice than in mice expressing wild‐type α3GlyRs (GlyRα3(WT) mice), but so were those of GABAergic IPSCs. Decreased frequencies of spontaneously occurring glycinergic and GABAergic miniature IPSCs (mIPSCs) with no accompanying change in mIPSC amplitudes suggested a change in presynaptic transmitter release. Paired‐pulse experiments on glycinergic IPSCs revealed an increased paired‐pulse ratio and a smaller coefficient of variation in GlyRα3(S346A) mice, which together indicate a reduction in transmitter release probability and an increase in the number of releasable vesicles. Paired‐pulse ratios of GABAergic IPSCs recorded in the presence of strychnine were not different between genotypes, while the coefficient of variation was smaller in GlyRα3(S346A) mice, demonstrating that the decrease in release probability was readily reversible by GlyR blockade, while the difference in the size of the pool of releasable vesicles remained. Taken together, our results suggest that presynaptic α3 GlyRs regulate synaptic glycine and GABA release in superficial dorsal horn neurons, and that this effect is potentially regulated by their phosphorylation status.

image

Key points

A serine‐to‐alanine point mutation was introduced into the glycine receptor α3 subunit of mice.

This point mutation renders α3 glycine receptors resistant to protein kinase A mediated phosphorylation but has otherwise only small effects on receptor function.

Patch‐clamp recordings from neurons in mouse spinal cord slices revealed an unexpected increase in the amplitudes of both glycinergic and GABAergic evoked inhibitory postsynaptic currents (IPSCs).

Miniature IPSCs, paired‐pulse ratios and synaptic variation analyses indicate a change in synaptic glycine and GABA release.

The results strongly suggest that α3 subunit‐containing glycine receptors are expressed on presynaptic terminals of inhibitory dorsal horn neurons where they regulate transmitter release.
A Medieval Drawbridge Pit and the Stories it Tells Us, Excavations at Pontefract Castle, 2019–2020
Authors: Jackson Nat , Casswell Chris , Forster Manda
Published: August 2023

DigVentures was commissioned by Wakefield Metropolitan District Council (WMDC) to undertake a programme of archaeological investigations as part of the Gatehouse Project, a community-focused archaeological research project based at Pontefract Castle, West Yorkshire. The social impact of the archaeological investigations, including project outcomes for heritage, for people and for the community, have been analysed and published in an earlier article. This article focuses on the archaeological evidence recovered during the excavations, and the conclusions drawn about the construction and chronology of the gatehouse at this part of the site.
Three-dimensional observations of tidal plume fronts in estuaries using a synthetic aperture sonar array
Authors: Marston Timothy M. , Bassett Christopher , Plotnick Daniel S. , Kidwell Autumn N. , Honegger David A.
Published: August 2023

Synthetic aperture sonar (sas) systems are designed to observe stationary scatterers located near the sediment interface. Less commonly, a sas system may be used to observe scattering features located above the sonar in the water column. The Undersea Remote Sensing (USRS) project, sponsored by the Office of Naval Research, was a collaborative Directed Research Initiative (DRI) focused on studying dynamic estuarine water column features. During the USRS DRI, researchers from multiple institutions gathered to observe tidal features at various estuaries along the coast of the United States using both in situ and remote sensing techniques, including sas. The first studied estuary was the mouth of the Connecticut River (CTR). Data captured by a sas system deployed during a tidal event were post-processed to create three-dimensional observations of the structure of the leading edge of the CTR's ebb plume front. From these observations, lobed structures similar in scale to previously reported instabilities are revealed, with the present observations providing additional insight regarding the structure of the bubble distribution behind the front. Velocity estimates of plume features were also determined from sas data and shown to compare favorably with concurrent marine radar estimates.
The Efficacy of Dry Needling in Combination With Electrical Stimulation on Pain Reduction and Improved Function in Chronic Plantar Heel Pain: A Critically Appraised Topic
Authors: Lumpkin Kelly J. , Fuchs Eric J. , Lowes Jeff N.
Published: August 2023

Focused Clinical Question: What is the efficacy of dry needling (DN) in combination with electrical stimulation on pain and function when compared with DN alone, conservative care, or placebo treatments for chronic plantar heel pain? Clinical Bottom Line: Based on a review of three good-quality randomized controlled trials, it appears the lasting effects of utilizing DN in combination with electrical stimulation on chronic plantar heel pain for reduction in pain and an increase in function are superior in some outcome measures but not all outcome measures over time as compared with other treatments. It is unclear whether DN in combination with electrical stimulation is superior to DN alone; however, both are clinically useful when used adjunctively more than four times in a month. Based on conflicting results, needling protocol variations, treatment type comparison variations, and good-quality studies, the grade of a B is assigned to this critically appraised topic.
A Narrative Review of Personalized Musculoskeletal Modeling Using the Physiome and Musculoskeletal Atlas Projects
Authors: Fernandez Justin , Shim Vickie , Schneider Marco , Choisne Julie , Handsfield Geoff , Yeung Ted , Zhang Ju , Hunter Peter , Besier Thor
Published: August 2023

In this narrative review, we explore developments in the field of computational musculoskeletal model personalization using the Physiome and Musculoskeletal Atlas Projects. Model geometry personalization; statistical shape modeling; and its impact on segmentation, classification, and model creation are explored. Examples include the trapeziometacarpal and tibiofemoral joints, Achilles tendon, gastrocnemius muscle, and pediatric lower limb bones. Finally, a more general approach to model personalization is discussed based on the idea of multiscale personalization called scaffolds.
Identity and Discourse Among #ActuallyAutistic Twitter Users With Motor Differences
Authors: Chatterjee Riya , Fears Nicholas E. , Lichtenberg Gavin , Tamplain Priscila M. , Miller Haylie L.
Published: August 2023

Despite a growing awareness of the prevalence of motor differences in the autistic community, their functional impact is poorly understood. Social media offers the ideal setting to observe this discourse in a less-contrived setting than lab-based structured interviews. The aims of the present study were (a) to determine the proportion of Twitter users who self-identify as autistic and dyspraxic/having developmental coordination disorder, relative to autistic alone, and (b) to identify common themes emerging from two moderated chat threads with motor-related prompts. Using the Twitter research application programming interface, we harvested data from users’ public profiles and tweets containing terms related to autism and developmental coordination disorder within a 1-month time period. We also harvested data from two #AutChat threads related to motor skills, which included 151 tweets from 31 unique autistic users (two with co-occurring developmental coordination disorder). Of these tweets, 44 were explicitly about motor differences, while the remainder consisted of discussion topics more loosely associated with motor skills. The following common themes were quantified: manual dexterity, lower extremity, oral motor, gross motor, posture, balance, stimming, movement pain, and coordination. Together, these findings indicate that motor differences are highly recognized and discussed among autistic individuals but are not overtly integrated into their identities at the same rate.
Convergent activation of Ca
2+
permeability in two-pore channel 2 through distinct molecular routes
Authors: Saito Ryo , Mu Qianru , Yuan Yu , Rubio-Alarcón Marcos , Eznarriaga Maria , Zhao Pingwei , Gunaratne Gihan , Kumar Sushil , Keller Marco , Bracher Franz , Grimm Christian , Brailoiu Eugen , Marchant Jonathan S. , Rahman Taufiq , Patel Sandip
Published: August 2023

TPC2 is a pathophysiologically relevant lysosomal ion channel that is activated directly by the phosphoinositide PI(3,5)P
2
and indirectly by the calcium ion (Ca
2+
)–mobilizing molecule NAADP through accessory proteins that associate with the channel. TPC2 toggles between PI(3,5)P
2
-induced, sodium ion (Na
+
)–selective and NAADP-induced, Ca
2+
–permeable states in response to these cues. To address the molecular basis of polymodal gating and ion-selectivity switching, we investigated the mechanism by which NAADP and its synthetic functional agonist, TPC2-A1-N, induced Ca
2+
release through TPC2 in human cells. Whereas NAADP required the NAADP-binding proteins JPT2 and LSM12 to evoke endogenous calcium ion signals, TPC2-A1-N did not. Residues in TPC2 that bind to PI(3,5)P
2
were required for channel activation by NAADP but not for activation by TPC2-A1-N. The cryptic voltage-sensing region of TPC2 was required for the actions of TPC2-A1-N and PI(3,5)P
2
but not for those of NAADP. These data mechanistically distinguish natural and synthetic agonist action at TPC2 despite convergent effects on Ca
2+
permeability and delineate a route for pharmacologically correcting impaired NAADP-evoked Ca
2+
signals.
The gliogenic switch takes teamwork
Authors: Ferrarelli Leslie K.
Published: August 2023

A five-signal cue drives the switch to glia production in the developing fetal brain.
Comparison of analytical sensitivity of DNA-based and RNA-based nucleic acid amplification tests for reproductive tract infection pathogens: implications for clinical applications
Authors: Ma Yu , Jiang Jian , Han Yanxi , Chen Yuqing , Diao Zhenli , Huang Tao , Feng Lei , Chang Lu , Wang Duo , Zhang Yuanfeng , Li Jinming , Zhang Rui
Published: August 2023

Currently, DNA-based nucleic acid amplification tests (NAATs) and RNA-based NAATs are employed to detect reproductive tract infection (RTI) pathogens including
Chlamydia trachomatis
(
CT
),
Neisseria gonorrhoeae
(
NG
), and
Ureaplasma urealyticum
(
UU
). Although evaluations of DNA-based NAATs have already existed, the comparison of the two methods is scarce. Thus, we compared the limits of detection (LODs) of DNA-based and RNA-based NAATs on the same experimental conditions. Inactivated culture supernatants of
CT
,
NG,
and
UU
with determined pathogen DNA and RNA load were used to evaluate LODs of seven DNA kits and one RNA kit. The LODs of the seven DNA kits for
CT
,
NG,
and
UU
ranged between 38–1,480, 94–20,011, and 132–2,011 copies/mL, respectively. As for RNA kits, they could detect samples at RNA concentrations of 3,116, 2,509, and 2,896 copies/mL, respectively. The RNA concentrations of
CT
,
NG
, and
UU
were 40, 885, and 42 times that of corresponding pathogen DNA concentrations in the employed supernatants, so RNA kits could detect pathogen DNA concentrations as low as 78 copies/mL, 3 copies/mL, and 69 copies/mL, respectively, but the level of pathogen load that the RNA tests could detect was primarily dependent on the infectious phase and transcriptional level of RNA. Thus, a schematic of bacterial dynamics during the period of reproductive tract infections was provided, which suggests that in terms of the analytical sensitivity of pathogen detection, RNA tests are more suitable for detecting active infection and recovery phase, while DNA tests are more suitable for detection in the early stage of infection.

IMPORTANCE

Reproductive tract infections have considerable effects on the health of humans.
CT
,
NG
, and
UU
are common pathogens. Although evaluation of DNA-based tests has already existed, the comparison between DNA-based and RNA-based tests is rare. Therefore, this study compared the limits of detection of the two tests on the same experimental conditions. Results suggested that most DNA-based NAATs could detect
CT
,
NG
, and
UU
at DNA concentrations lower than 1,000 copies/mL, while RNA-based NAATs could detect bacteria at RNA concentrations around 3,000 copies/mL. Considering the copy number of RNA per bacterium is dynamic through the growth cycle, further comparison is combined with a schematic of bacterial dynamics. Results suggested that in terms of the analytical sensitivity of pathogen detection, RNA tests are more suitable for detecting active infection and recovery phase, while DNA tests are more suitable for detection in the early stage of infection.
Supplemental Material: Icy thermometers: Quantifying the impact of volcanic heat on glacier elevation
Authors: Howcutt Stephen , Spagnolo Matteo , al. et
Published: August 2023

Further methodological details and tabular data of analyzed volcanoes and glaciers.  
Electroresponsive Materials for Soft Robotics
Authors: Kuznetsov N. M. , Banin E. P. , Krupnin A. E. , Krasheninnikov S. V. , Chichaev I. A. , Koroteev A. V. , Grigoriev T. E. , Chvalun S. N.
Published: August 2023

The review considers the main approaches to the development of structural and active elements for actuators in soft robotics. An analysis of publications in the field of recent achievements in electroresponsive polymer materials operating on the principles of Maxwell pressure and electrostriction is provided. The main problems of the development of locomotor elements for soft robotics in terms of the design and structural analysis of actuators, and methods of activating the locomotor function, are noted. Moreover, some issues related to promising materials for soft robotics and methods for their production are considered. Great emphasis in the review is placed on an integrated approach and modern methods in the study of materials, including the use of mega-science facilities. Modern technological approaches to the design and manufacturing of soft-robotic devices are outlined. Appropriate analytical and numerical methods that allow relevant material models to be obtained for a comprehensive description of the behavior of actuators for soft robotics are considered. An overview of the functional prototypes of soft robots, designed according to the principle of nature-likeness, with active elements made of electroresponsive polymer materials is presented.
Model of Multifilamentary Resistive Switching for a Memristor with Hopping Conductivity
Authors: Demin V. A. , Ilyasov A. I. , Rylkov V. V. , Kashkarov P. K. , Kovalchuk M. V.
Published: August 2023

Many applications, including learning neuromorphic computing systems, require the analogue or, at least, multilevel resistive switching (RS) of memristor devices. In metal–insulator–metal (MIM) structures it is often associated with the creation of a large number of conductive channels, or filaments, but in the majority of cases, especially for the vacancy mechanism of RS, the direct observation of many filaments is difficult or impossible. In this work, a model of the explicit filament conductivity distribution for a nanocomposite (NC) LiNbO3-based memristor, that nonetheless may be applicable to other types of MIM memristors with hopping conductivity over dangling bonds in an amorphous insulator layer, is derived from physical principles. This model, in addition to indirect evidence from magnetic and capacitance measurements, reaffirms the multifilamentary RS mechanism by the approximation of experimental data on synaptic plasticity, i.e., a change in the conductivity of a memristor by a pair of pulses applied to it. The results of this research offer opportunities to study RS in MIM structures at the macroscopic level using model filament distributions and substantiates the possibility of successfully applying the considered NC memristors as synaptic elements of neuromorphic networks.
Voices of society: the emergence of civil-society practices aiming to engage in the management of the COVID-19 pandemic in the Netherlands
Authors: Kemper Sophie , van den Broek Renate , van Hameren Sarah , Kupper J Frank H , Bongers Marloes E J , de Weger Esther , de Vries Marion , Timen Aura
Published: August 2023

During the COVID-19 pandemic, public groups mobilised themselves in civil-society engagement practices (CSEPs) aiming to improve or suggest alternative epidemic management. This study explores the motivation to establish CSEPs and their perceived contributions to epidemic management, to gain insight whether integrating views of CSEPs could add value. A systematic online search was executed to identify CSEPs focused on COVID-19 management between January 2020 and January 2022 in the Netherlands. In order to create a comprehensible overview of the identified CSEPs, relevant characteristics were gathered and mapped, for example, local or national scope, subject of action and goals. A selection of CSEPs was interviewed between April and June 2022 to study their motivators to start the CSEPs and perceived contributions to management. The search resulted in the identification of 22 CSEPs, of which members of 14 CSEPs were interviewed. These members indicated several issues that motivated the start of their CSEP, namely; shortage of equipment, sense of solidarity, and a perceived lack of governmental action, lack of democratic values and lack in diversity of perspectives in epidemic management. All respondents believed to have contributed to policy or society, by influencing opinions, and occasionally by altering policy. However, respondents encountered obstacles in their attempts to contribute such as inability to establish contact with authorities, feeling unheard or undermined, and complications due to the interplay of political interests. In conclusion, CSEPs have fulfilled various roles such as providing alternative management policies, producing equipment, representing the needs of vulnerable populations, and supporting citizens and providing citizens with other viewpoints and information. The identified motivators to establish CSEPs in this study uncover room for improvements in policy. These insights, together with the identified perceived barriers of CSEPs, can be used to improve the connection between (future) epidemic management and public priorities and interests.
Exercise electrocardiography for pre-test assessment of the likelihood of coronary artery disease
Authors: Rasmussen Laust Dupont , Schmidt Samuel Emil , Knuuti Juhani , Newby David E , Singh Trisha , Nieman Koen , Galema Tjebbe W , Vrints Christiaan , Bøttcher Morten , Winther Simon
Published: August 2023

Objectives

To develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD).

Methods

An ExECG-weighted clinical likelihood (ExECG-CL) model was developed in a training cohort of patients with suspected obstructive CAD undergoing ExECG. Next, the ExECG-CL model was applied in a CAD validation cohort undergoing ExECG and clinically driven invasive coronary angiography and a prognosis validation cohort and compared with the risk factor-weighted clinical likelihood (RF-CL) model for obstructive CAD discrimination and prognostication, respectively.

In the CAD validation cohort, obstructive CAD was defined as >50% diameter stenosis on invasive coronary angiography. For prognosis, the endpoint was non-fatal myocardial infarction and death.

Results

The training cohort consisted of 1214 patients (mean age 57 years, 57% males). In the CAD (N=408; mean age 55 years, 53% males) and prognosis validation (N=3283; mean age 57 years, 57% males) cohorts, 11.8% patients had obstructive CAD and 4.4% met the endpoint. In the CAD validation cohort, discrimination of obstructive CAD was similar between the ExECG-CL and RF-CL models: area under the receiver-operating characteristic curves 83.1% (95% CIs 77.5% to 88.7%) versus 80.7% (95% CI 74.6% to 86.8%), p=0.14. In the ExECG-CL model, more patients had very low (≤5%) clinical likelihood of obstructive CAD compared with the RF-CL (42.2% vs 36.0%, p<0.01) where obstructive CAD prevalence and event risk remained low.

Conclusions

ExECG incorporated into a clinical likelihood model improves reclassification of patients to a very low clinical likelihood group with very low prevalence of obstructive CAD and favourable prognosis.
Id-neoantigen vaccine induces therapeutic CD8+T cells against multiple myeloma: H chain-loss escapees cause FLC MM
Authors: Westhrin Marita , Blazevski Jana , Textor Ana , Abdollahi Pegah , Gopalakrishnan Ramakrishna Prabhu , Ngo Linda Thuy , Hofgaard Peter Olaf , Heinzelbecker Julia , Bobic Sonja , Fossum Even , Spång Heidi Cecilie Larsen , Braathen Ranveig , Bogen Bjarne
Published: August 2023

Background

Multiple myeloma (MM) cancers originate from plasma cells that have passed through the germinal center reaction where somatic hypermutation of Ig V regions takes place. Myeloma protein V regions often express many mutations and are thus a rich source of neoantigens (traditionally called idiotopes (Id)). Therefore, these are highly tumor-specific and excellent targets for immunotherapy.

Methods

We have developed a DNA Id vaccine which as translated protein targets conventional dendritic cells (cDC) for CCL3-mediated delivery of myeloma protein V regions in a single-chain fragment variable (scFv) format. Vaccine efficacy was studied in the mouse MM model, mineral oil-induced plasmacytoma 315.BM.

Results

The Id vaccine protected mice against a challenge with MM cells. Moreover, the vaccine had a therapeutic effect. However, in some of the vaccinated mice, MM cells not producing H chains escaped rejection, resulting in free light chain (FLC) MM. Depletion of CD8+T cells abrogated vaccine efficacy, and protection was observed to be dependent on cDC1s, using Batf3-/-mice. Modifications of scFv in the vaccine demonstrated that CD8+T cells were specific for two mutated VHsequences.

Conclusions

VHneoantigen-specific CD8+T cells elicited by CCL3-containing Id vaccines had a therapeutic effect against MM in a mouse model. MM cells could escape rejection by losing expression of the H chain, thus giving rise to FLC MM.
Antitumor immunity as the basis for durable disease-free treatment-free survival in patients with metastatic urothelial cancer
Authors: Anker Jonathan , Pal Sumanta K , Kim-Schulze Seunghee , Wang Huan , Halperin Rebecca , Uzilov Andrew , Imai Naoko , Eikawa Shingo , Saito Takuro , Sebra Robert , Hahn Noah M , Patel Manishkumar , Qi Jingjing , Xie Hui , Bhardwaj Nina , Gnjatic Sacha , Galsky Matthew D
Published: August 2023

Cisplatin-based chemotherapy has been associated with durable disease control in a small subset of patients with metastatic urothelial cancer. However, the mechanistic basis for this phenomenon has remained elusive. Antitumor immunity may underlie these exceptional responders. In a phase II trial evaluating a phased schedule of gemcitabine and cisplatin followed by gemcitabine and cisplatin with ipilimumab for metastatic urothelial cancer, 4 of 36 patients achieved durable disease-free treatment-free survival (DDFTFS) and remain in remission over 5 years after enrolment on the study. We sought to identify the genomic and immunological mechanisms associated with functional cures of such patients. Whole exome sequencing was performed on pretreatment archival tumor tissue. Neoantigen prediction and ranking were performed using a novel pipeline. For a subset of patients with available biospecimens, selected peptides were tested for neoantigen-specific T cell reactivity in peripheral blood CD4+and CD8+T cells cultured with autologous antigen-presenting cells at baseline, postchemotherapy, and postchemotherapy and ipilimumab timepoints. Multiplex assays of serum protein analytes were also assessed at each time point. Serum proteomic analysis revealed that pretreatment, patients achieving DDFTFS demonstrated an immune activated phenotype with elevations in TH1 adaptive immunity, costimulatory molecules, and immune checkpoint markers. After combination cisplatin-based chemotherapy and ipilimumab treatment, DDFTFS patients again displayed enrichment for markers of adaptive immunity, as well as T cell cytotoxicity. CD27 was uniquely enriched in DDFTFS patients at all timepoints. Neoantigen reactivity was not detected in any patient at baseline or post two cycles of chemotherapy. Both CD4+and CD8+neoantigen-specific T cell reactivity was detected in two of two DDFTFS patients in comparison to zero of five non-DDFTFS patients after combination cisplatin-based chemotherapy and ipilimumab treatment. Antitumor immunity may underlie functional cures achieved in patients with metastatic urothelial cancer treated with cisplatin-based chemotherapy and immune checkpoint blockade. Probing the mechanistic basis for DDFTFS may facilitate the identification of biomarkers, therapeutic components, and optimal treatment sequences necessary to extend this ultimate goal to a larger subset of patients.