bluuebunny/crossref_metadata_2025 huggingface dataset:
Building and changing business models: a qualitative study among Dutch physiotherapy primary healthcare organisations
Authors: IJntema Rutger , Barten Di-Janne , Duits Hans , Tjemkes Brian , Veenhof Cindy
Published: March 2022

Aim:

To gain insights into what business model-building and model-changing aspects make physiotherapy primary healthcare organisations (PTPHOs) attain and sustain superior performance in a changing environment, according to their managers.

Background:

Since 2006, the transition towards managed competition in the Dutch healthcare market has been intended to improve the performance of primary healthcare organisations like PTPHOs. In such a market, competition on efficiency with reimbursement system has been introduced. Consequently, performance entails achieving and sustaining quality, efficiency, and financial outcomes. Superior performance requires that PTPHOs continuously align their external environment and internal organisation. The business model literature suggests that business model-building and model-changing support this alignment process.

Methods:

This qualitative study had an explorative design. A pre-defined interview guide based on business model theory was applied. Semi-structured interviews were conducted with physiotherapy primary healthcare organisation managers and transcribed verbally. The transcripts were analysed using directed content analysis.

Findings:

The study results show, both verbally and graphically, that PTPHOs generate superior performance in a changing environment through business model-building and model-changing. Participating managers (n = 25) confirmed extant findings that business model-building consists of strategy and business model configuration. In addition, business model-building entails establishing interfaces to exploit external environment and internal organisation information. Also, these interfaces are evaluative techniques and tools, action, and process – make sense of knowledge and information. To sustain superior performance, it is essential to change the business model. This can be achieved through three change cycles: business model change, short-term change, and long-term change.

Conclusion:

Managers of both superior and lower performance organisations independently stress the importance of the same business model-building and model-changing aspects related to attainment and sustainment of superior performance. However, superior performance PTPHOs address building and changing business models in a more diversified and integrated way than their lower performance counterparts.
Integrated primary health care services in two protracted refugee camp settings at the Thai–Myanmar border 2000–2018: trends on mortality and incidence of infectious diseases
Authors: Mohr Oliver , Benner Marie T. , Sansoenboon Ammarat , Kaloy Wiphan , McGready Rose , Carrara Verena I.
Published: March 2022

Aim:

This study aimed to assess the health outcome of four epidemic-prone infectious diseases, in the context of a Primary Health Care project implemented in a protracted refugee setting along the Thai–Myanmar border.

Background:

Refugees settled at the Thai–Myanmar border are fully dependent on support for health services, shelter, food, education, water, and sanitation. The Non-Governmental Organization Malteser International developed an integrated Primary Health Care program in close cooperation with trained camp residents over 25 years in the two settlements under its supervision. The project has been funded by the European Commission Civil Protection and Humanitarian Aid Operations (DG ECHO).

Methods:

This was a retrospective primary health care project evaluation. All-cause mortality; morbidity trends in malaria, lower respiratory tract infections (LRTIs), watery diarrhea, and dysentery; and health service utilization covering a time span of 18 years were assessed. Programmatic changes in the Primary Health Care (PHC) project and events with a potential effect on health of the target population were examined.

Findings:

Despite the continuous drain of trained health care workers, the volatile influx of refugees, and the isolated location of the two camps, the initial basic curative health care developed into an integrated and comprehensive PHC project including a SPHERE-compliant water, sanitation, and hygiene program. Malaria, LRTIs, watery diarrhea, and dysentery morbidity dropped twelve, three, two, and fivefold, respectively, over the 18-year period evaluated while the health services utilization dropped from 7.1 to 2.9 consultations per refugee/year. The international community may face situations where integration of refugees into the health services of the host country is not possible. In such a context, integrated and evidence-based PHC adequately funded and implemented by one health agency is an effective and relevant approach to reduce the infectious diseases burden under the constraints of semipermanent living conditions.
The Role of Procedural Justice in Policing
Authors: Pryce Daniel K. , Whitaker Ingrid Phillips
Published: March 2022

Empirical studies have pointed to the increasing importance of procedural justice as a tool for improving the relationship between the police and local communities. The mediating role of procedural justice continues to be embraced by scholars, practitioners, and community members; as a result, we examine in the present study African Americans’ attitudes toward the police via the interpretive lens of procedural justice policing. Using procedural justice questions found in the social-psychology literature, we interviewed seventy-seven African Americans in Durham, NC, to assess their views about the U.S. police. Our results point to the following for improving the relationship between the police and African Americans: respect for African Americans by police, police fairness in the African American community, and increased and improved interaction between police and African Americans. Notably, these findings spanned three distinct educational and socioeconomic spectrums. The implications of our findings for community relations, public policy, and future research are discussed.
Global regulatory competition on digital rights and data protection: A novel and contractive form of Eurocentrism?
Authors: Çapar Gürkan
Published: March 2022

Global regulatory competition is a recent phenomenon that confronts us in various different fields, ranging from food and chemical safety to climate change, and animal welfare to environmental law. The digital economy is not immune to this trend, and it seems highly unlikely that this will soon come to an end when we consider the radical differences between the European Union and the United States with respect to the importance they assign to the right to privacy and the right to freedom of speech. Nevertheless, despite their differences in content, it can be contended that they both tend to disregard the interest of others even though they have enough resources at their disposal to take them seriously. This becomes visible when the recent case law of the CJEU and the recent regulations such as the GDPR and the US CLOUD Act are taken into account. Their similar attitude to regulating for the globe raises the question of whether we are confronted with a new type of Eurocentrism, which is more contracted and introverted than the previous expansionist version. The article argues that unilateralism should be a selfless one and that it should necessarily consider outsiders if it is to acquire legitimacy.
Ocean Sound Propagation in a Changing Climate: Global Sound Speed Changes and Identification of Acoustic Hotspots
Authors: Affatati Alice , Scaini Chiara , Salon Stefano
Published: March 2022

Climate change is a relevant threat on a global scale, leading to impacts on ecosystems and ocean biodiversity. A considerable fraction of marine life depends on sound. Marine mammals, in particular, exploit sound in all aspects of their life, including feeding and mating. This work explores the impact of climate change in sound propagation by computing the three‐dimensional global field of underwater sound speed. The computation was performed based on present conditions (2006–2016) and a “business‐as‐usual” future climate scenario (Representative Concentration Pathway 8.5), identifying two “acoustic hotspots” where larger sound speed variations are expected. Our results indicate that the identified acoustic hotspots will present substantial climate‐change‐induced sound speed variations toward the end of the century, potentially affecting the vital activities of species in the areas. Evidence is provided of the impact of such variation on underwater sound transmission. As an example of a species impacted by underwater transmission, we considered one marine mammal endangered species, the North Atlantic right whale (Eubalaena glacialis), in the northwestern Atlantic Ocean. To the best of our knowledge, this is the first global‐scale data set of climate‐induced sound speed changes expected under a future scenario. This study provides a starting point for policies oriented research to promote the conservation of marine ecosystems and, in particular, endangered marine mammals.
A Decreasing Trend of Nitrous Oxide Emissions From California Cropland From 2000 to 2015
Authors: Deng Jia , Guo Lei , Salas William , Ingraham Pete , Charrier‐Klobas Jessica G. , Frolking Steve , Li Changsheng
Published: March 2022

Mitigation of greenhouse gas emissions from agriculture requires an understanding of spatial‐temporal dynamics of nitrous oxide (N2O) emissions. Process‐based models can quantify N2O emissions from agricultural soils but have rarely been applied to regions with highly diverse agriculture. In this study, a process‐based biogeochemical model, DeNitrification‐DeComposition (DNDC), was applied to quantify spatial‐temporal dynamics of direct N2O emissions from California cropland employing a wide range of cropping systems. DNDC simulated direct N2O emissions from nitrogen (N) inputs through applications of synthetic fertilizers and crop residues during 2000–2015 by linking the model with a spatial‐temporal differentiated database containing data on weather, crop areas, soil properties, and management. Simulated direct N2O emissions ranged from 3,830 to 7,875 tonnes N2O‐N yr−1, representing 0.73%–1.21% of the N inputs. N2O emission rates were higher for hay and field crops and lower for orchard and vineyard. State cropland total N2O emissions showed a decreasing trend primarily driven by reductions of cropland area and N inputs, the trend toward growing more orchard, and changes in irrigation. Annual direct N2O emissions declined by 47% from 2000 to 2015. Simulations showed N2O emission variations could be explained not only by cropland area and N fertilizer inputs but also climate, soil properties, and management besides N fertilization. The detailed spatial‐temporal emission dynamics and driving factors provide knowledge toward effective N2O mitigation and highlight the importance of coupling process‐based models with high‐resolution data for characterizing the spatial‐temporal variability of N2O emissions in regions with diverse croplands.
A Statistical Study of Poleward Traveling Ionospheric Disturbances Over the African and American Sectors During Geomagnetic Storms
Authors: Habarulema John Bosco , Thaganyana Golekamang P. , Katamzi‐Joseph Zama T. , Yizengaw Endawoke , Moldwin Mark B. , Ngwira Chigomezyo M.
Published: March 2022

We present statistical results of traveling ionospheric disturbances (TIDs) with origin near the geomagnetic equator during geomagnetic storms that occurred within the period of 2010–2018. Based on storm criteria of Kp > 4 and Dst ≤ −50 nT, we have analyzed total electron content perturbations derived from Global Navigational Satellite Systems observations within a latitude range of 40°S–60°N and longitude ranges of 20°–40°E and 50°–70°W representing the African and American sectors. Although the northern hemispheric part of the African sector has limited data coverage, results show that the launched TIDs do not exceed the latitudinal distance of 20°–25° from their origin during the analyzed period. A statistically similar result is observed over the American sector with launched poleward TIDs constrained largely within ±20°–30° around the geomagnetic equator. Where data are available, majority of these cases are linked to changes in ionospheric electrodynamics, especially the enhancement of equatorial electrojet (EEJ), although there are other observations that are not explained by EEJ variability. This indicates that there may be other physical mechanisms that play a role in launching TIDs at the geomagnetic equator during disturbed conditions. An important result is that large‐scale and medium‐scale TIDs have been found to occur predominantly during the main and recovery phases of geomagnetic storms, respectively, at least over the African sector.
Multi‐Scale Density Structures in the Plasmaspheric Plume During a Geomagnetic Storm
Authors: Nishimura Y. , Goldstein J. , Martinis C. , Ma Q. , Li W. , Zhang S. R. , Coster A. J. , Mrak S. , Semeter J. L. , Nishitani N. , Ruohoniemi J. M. , Shepherd S. G.
Published: March 2022

Evolution of large‐scale and fine‐scale plasmaspheric plume density structures was examined using space‐ground coordinated observations of a plume during the 7–8 September 2015 storm. The large‐scale plasmaspheric plume density at Van Allen Probes A was roughly proportional to the total electron content (TEC) along the satellite footprint, indicating that TEC distribution represents the large‐scale plume density distribution in the magnetosphere. The plasmaspheric plume contained fine‐scale density structures and subauroral polarization streams (SAPS) velocity fluctuations. High‐resolution TEC data support the interpretation that the fine‐scale plume structures were blobs with ∼300 km size and ∼500–800 m/s in the ionosphere (∼3,000 km size and ∼5–8 km/s speed in the magnetosphere), emerging at the plume base and drifting to the plume. The short‐baseline Global Navigation Satellite System receivers detected smaller‐scale (∼10 km in the ionosphere, ∼100 km in the magnetosphere) TEC gradients and their sunward drift. Fine‐scale density structures were associated with enhanced phase scintillation index. Velocity fluctuations were found to be spatial structures of fine‐scale SAPS flows that drifted sunward with density irregularities down to ∼10 s of meter‐scale. Fine‐scale density structures followed a power law with a slope of ∼−5/3, and smaller‐scale density structures developed slower than the larger‐scale structures. We suggest that turbulent SAPS flows created fine‐scale density structures and their cascading to smaller scales. We also found that the plume fine‐scale density structures were associated with whistler‐mode intensity modulation, and localized electron precipitation in the plume. Structured precipitation in the plume may contribute to ionospheric heating, SAPS velocity reduction, and conductance enhancements.
Strong Margin Influence on the Arctic Ocean Barium Cycle Revealed by Pan‐Arctic Synthesis
Authors: Whitmore Laura M. , Shiller Alan M. , Horner Tristan J. , Xiang Yang , Auro Maureen E. , Bauch Dorothea , Dehairs Frank , Lam Phoebe J. , Li Jingxuan , Maldonado Maria T. , Mears Chantal , Newton Robert , Pasqualini Angelica , Planquette Hélène , Rember Robert , Thomas Helmuth
Published: March 2022

Early studies revealed relationships between barium (Ba), particulate organic carbon and silicate, suggesting applications for Ba as a paleoproductivity tracer and as a tracer of modern ocean circulation. But, what controls the distribution of barium (Ba) in the oceans? Here, we investigated the Arctic Ocean Ba cycle through a one‐of‐a‐kind data set containing dissolved (dBa), particulate (pBa), and stable isotope Ba ratio (δ138Ba) data from four Arctic GEOTRACES expeditions conducted in 2015. We hypothesized that margins would be a substantial source of Ba to the Arctic Ocean water column. The dBa, pBa, and δ138Ba distributions all suggest significant modification of inflowing Pacific seawater over the shelves, and the dBa mass balance implies that ∼50% of the dBa inventory (upper 500 m of the Arctic water column) was supplied by nonconservative inputs. Calculated areal dBa fluxes are up to 10 μmol m−2 day−1 on the margin, which is comparable to fluxes described in other regions. Applying this approach to dBa data from the 1994 Arctic Ocean Survey yields similar results. The Canadian Arctic Archipelago did not appear to have a similar margin source; rather, the dBa distribution in this section is consistent with mixing of Arctic Ocean‐derived waters and Baffin Bay‐derived waters. Although we lack enough information to identify the specifics of the shelf sediment Ba source, we suspect that a sedimentary remineralization and terrigenous sources (e.g., submarine groundwater discharge or fluvial particles) are contributors.
The Annual Salinity Cycle of the Denmark Strait Overflow
Authors: Opher J. G. , Brearley J. A. , Dye S. R. , Pickart R. S. , Renfrew I. A. , Harden B. E. , Meredith M. P.
Published: March 2022

The Denmark Strait Overflow (DSO) is an important source of dense water input to the deep limb of the Atlantic Meridional Overturning Circulation (AMOC). It is fed by separate currents from the north that advect dense water masses formed in the Nordic Seas and Arctic Ocean which then converge at Denmark Strait. Here we identify an annual salinity cycle of the DSO, characterized by freshening in winter and spring. The freshening is linked to freshening of the Shelfbreak East Greenland Current in the Blosseville Basin north of the Denmark Strait. We demonstrate that the East Greenland Current advects fresh pycnocline water above the recirculating Atlantic Water, which forms a low salinity lid for the overflow in Denmark Strait and in the Irminger Basin. This concept is supported by intensified freshening of the DSO in lighter density classes on the Greenland side of the overflow. The salinity of the DSO in the Irminger Basin is significantly correlated with northerly/northeasterly winds in the Blosseville Basin at a lag of 3–4 months, consistent with estimated transit times. This suggests that wind driven variability of DSO source water exerts an important influence on the salinity variability of the downstream DSO, and hence the composition of the deep limb of the AMOC.
Measurement and Analysis of the Microphysical Properties of Arctic Precipitation Showing Frequent Occurrence of Riming
Authors: Fitch Kyle E. , Garrett Timothy J.
Published: March 2022

Detailed ground‐based observations of snow are scarce in remote regions, such as the Arctic. Here, Multi‐Angle Snowflake Camera measurements of over 55,000 solid hydrometeors—obtained during a two‐year period from August 2016 to August 2018 at Oliktok Point, Alaska—are analyzed and compared to similar measurements from an earlier experiment at Alta, Utah. In general, distributions of hydrometeor fall speed, fall orientation, aspect ratio, flatness, and complexity (i.e., riming degree) were observed to be very similar between the two locations, except that Arctic hydrometeors tended to be smaller. In total, the slope parameter defining a negative exponential of the size distribution was approximately 50% steeper in the Arctic as at Alta. Sixty‐six percent of particles were observed to be rimed or moderately rimed with some suggestion that riming is favored by weak boundary layer stability. On average, the fall speed of rimed particles was not notably different from aggregates. However, graupel density and fall speed increase as cloud temperatures approach the melting point.
Characterizing Sediment Flux of Deforming Glacier Beds
Authors: Hansen D. D. , Zoet L. K.
Published: March 2022

Deformation of subglacial sediment during basal slip shapes the beds of many fast‐flowing glaciers and ice streams. The resultant sediment flux impacts glacier dynamics and rates of subglacial erosion over a range of timescales, but its fundamental dependencies are not well understood. Using a cryogenic ring shear device, we conducted experiments to investigate the effects of both effective stress and slip speed on rates of till transport. Sediment fluxes were computed using digital image correlation from a photographic time series of the till bed. We find a near‐linear relationship between sediment flux and slip speed, but a non‐monotonic, double‐valued dependency of sediment flux on effective stress. Deformation primarily occurred in a thin shear band near the ice sole, the thickness of which could vary with both parameters. Coupling between ice and till increased at higher slip speeds and effective stresses and scaled the magnitude of the flow profile.
Diagnosing the Thickness‐Weighted Averaged Eddy‐Mean Flow Interaction From an Eddying North Atlantic Ensemble: The Eliassen‐Palm Flux
Authors: Uchida Takaya , Jamet Quentin , Dewar William K. , Le Sommer Julien , Penduff Thierry , Balwada Dhruv
Published: March 2022

The thickness‐weighted average (TWA) framework, which treats the residual‐mean flow as the prognostic variable, provides a clear theoretical formulation of the eddy feedback onto the residual‐mean flow. The averaging operator involved in the TWA framework, although in theory being an ensemble mean, in practice has often been approximated by a temporal mean. Here, we analyze an ensemble of North Atlantic simulations at mesoscale‐permitting resolution (1/12°). We therefore recognize means and eddies in terms of ensemble means and fluctuations about those means. The ensemble dimension being orthogonal to the temporal and spatial dimensions negates the necessity for an arbitrary temporal or spatial scale in defining the eddies. Eddy‐mean flow feedbacks are encapsulated in the Eliassen‐Palm (E‐P) flux tensor and its convergence indicates that eddy momentum fluxes dominate in the separated Gulf Stream. The eddies can be interpreted to contribute to the zonal meandering of the Gulf Stream and a northward migration of it in the meridional direction. Downstream of the separated Gulf Stream in the North Atlantic Current region, the interfacial form stress convergence becomes leading order in the E‐P flux convergence.
Just 15.5% of Global Coastline Remains Intact
Authors: Donovan Robin
Published: March 2022

Combining data from land and sea helps ecologists measure human impact.
The Surprising Greenhouse Gas That Caused Volcanic Summer
Authors: Cartier Kimberly
Published: March 2022

Extended periods of volcanism known as flood basalt eruptions lead to volcanic winters, which are often followed by an extended period of warming. But it was more than just carbon dioxide that warmed the globe.
Little Influence of Asian Anthropogenic Aerosols on Summer Temperature in Central East Asia Since 1960
Authors: Hua Wenjian , Dai Aiguo , Chen Haishan
Published: March 2022

Recent summer surface air temperature (SAT) variations over Central East Asia (CEA) have been influenced by greenhouse gas and aerosol forcing since 1960. But how CEA SAT responds to contrasting changes in Asian, and European and North American aerosol sources remains unclear. By analyzing observations and model simulations, here we show that aerosol‐forced summer SAT changes over CEA since 1960 come mostly from the effects of aerosols outside Asia, with relatively small influences from Asian aerosols. Unlike Europe, where direct and indirect aerosol effects on surface solar radiation drive the SAT long‐term trend and decadal variations, over CEA atmospheric circulation response to aerosols outside Asia plays an important role. Aerosol‐forced anomalous low‐level low pressure in mid‐latitude Eurasia may influence the SAT anomalies downstream over mid‐latitude Asia, including a warm anomaly around CEA. The results suggest that caution is needed in attributing SAT changes around CEA to anthropogenic aerosols from Asia.
A bioinspired bubble removal method in microchannels based on angiosperm xylem embolism repair
Authors: Guo Lihua , Liu Yuanchang , Ran Penghui , Wang Gang , Shan Jie , Li Xudong , Liu Chong , Li Jingmin
Published: March 2022

It is difficult to remove and eliminate bubbles in microchannels in many devices used in various biomedical fields, such as those needed for microfluidic immunoassays, point-of-care testing, and cell biology evaluations. Accumulated bubbles are associated with a number of negative outcomes, including a decrease in device sensitivity, inaccuracy of analysis results, and even functional failure. Xylem conduits of angiosperm have the ability to remove bubbles in obstructed conduits. Inspired by such an embolism repair mechanism, this paper proposes a bioinspired bubble removal method, which exhibits a prominent ability to dissolve bubbles continuously within a large range of flow rates (2 µL/min–850 µL/min) while retaining the stability and continuity of the flow without auxiliary equipment. Such a method also shows significant bubble removal stability in dealing with Newtonian liquids and non-Newtonian fluids, especially with high viscosity (6.76 Pa s) and low velocity (152 nL/min). Such advantages associated with the proposed bioinspired method reveal promising application prospects in macro/microfluidic fields ranging from 3D printing, implantable devices, virus detection, and biomedical fluid processing to microscale reactor operation and beyond.
Antibody drug conjugate: the “biological missile” for targeted cancer therapy
Authors: Fu Zhiwen , Li Shijun , Han Sifei , Shi Chen , Zhang Yu
Published: March 2022

Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as “biological missiles”, is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.
High-dose-androgen-induced autophagic cell death to suppress the Enzalutamide-resistant prostate cancer growth via altering the circRNA-BCL2/miRNA-198/AMBRA1 signaling
Authors: Chen Lei , Sun Yin , Tang Min , Wu Denglong , Xiang Zhendong , Huang Chi-Ping , You Bosen , Xie Dongdong , Ye Qinglin , Yu Dexin , Chang Chawnshang
Published: March 2022

Androgen deprivation therapy (ADT) is a gold standard treatment for advanced PCa. However, most patients eventually develop the castration-resistant prostate cancer (CRPC) that progresses rapidly despite ongoing systemic androgen deprivation. While early studies indicated that high physiological doses of androgens might suppress rather than promote PCa cell growth in some selective CRPC patients, the exact mechanism of this opposite effect remains unclear. Here we found that Enzalutamide-resistant (EnzR) CRPC cells can be suppressed by the high-dose-androgen (dihydrotestosterone, DHT). Mechanism dissection suggested that a high-dose-DHT can suppress the circular RNA-BCL2 (circRNA-BCL2) expression via transcriptional regulation of its host gene BCL2. The suppressed circRNA-BCL2 can then alter the expression of miRNA-198 to modulate the AMBRA1 expression via direct binding to the 3′UTR of AMBRA1 mRNA. The consequences of high-dose-DHT suppressed circRNA-BCL2/miRNA-198/AMBRA1 signaling likely result in induction of the autophagic cell death to suppress the EnzR CRPC cell growth. Preclinical studies using in vivo xenograft mouse models also demonstrated that AMBRA1-shRNA to suppress the autophagic cell death can weaken the effect of high-dose-DHT on EnzR CRPC tumors. Together, these in vitro and in vivo data provide new insights for understanding the mechanisms underlying high-dose-DHT suppression of the EnzR CRPC cell growth, supporting a potential therapy using high-dose-androgens to suppress CRPC progression in the future.
South-to-north migration preceded the advent of intensive farming in the Maya region
Authors: Kennett Douglas J. , Lipson Mark , Prufer Keith M. , Mora-Marín David , George Richard J. , Rohland Nadin , Robinson Mark , Trask Willa R. , Edgar Heather H. J. , Hill Ethan C. , Ray Erin E. , Lynch Paige , Moes Emily , O’Donnell Lexi , Harper Thomas K. , Kate Emily J. , Ramos Josue , Morris John , Gutierrez Said M. , Ryan Timothy M. , Culleton Brendan J. , Awe Jaime J. , Reich David
Published: March 2022

The genetic prehistory of human populations in Central America is largely unexplored leaving an important gap in our knowledge of the global expansion of humans. We report genome-wide ancient DNA data for a transect of twenty individuals from two Belize rock-shelters dating between 9,600-3,700 calibrated radiocarbon years before present (cal. BP). The oldest individuals (9,600-7,300 cal. BP) descend from an Early Holocene Native American lineage with only distant relatedness to present-day Mesoamericans, including Mayan-speaking populations. After ~5,600 cal. BP a previously unknown human dispersal from the south made a major demographic impact on the region, contributing more than 50% of the ancestry of all later individuals. This new ancestry derived from a source related to present-day Chibchan speakers living from Costa Rica to Colombia. Its arrival corresponds to the first clear evidence for forest clearing and maize horticulture in what later became the Maya region.
Incidence of brain metastases in patients with early HER2-positive breast cancer receiving neoadjuvant chemotherapy with trastuzumab and pertuzumab
Authors: Ferraro Emanuela , Singh Jasmeet , Patil Sujata , Razavi Pedram , Modi Shanu , Chandarlapaty Sarat , Barrio Andrea V. , Malani Rachna , Mellinghoff Ingo K. , Boire Adrienne , Wen Hannah Y. , Brogi Edi , Seidman Andrew D. , Norton Larry , Robson Mark E. , Dang Chau T.
Published: March 2022

The addition of pertuzumab (P) to trastuzumab (H) and neoadjuvant chemotherapy (NAC) has decreased the risk of distant recurrence in early stage HER2-positive breast cancer. The incidence of brain metastases (BM) in patients who achieved pathological complete response (pCR) versus those who do not is unknown. In this study, we sought the incidence of BM in patients receiving HP-containing NAC as well as survival outcome. We reviewed the medical records of 526 early stage HER2-positive patients treated with an HP-based regimen at Memorial Sloan Kettering Cancer Center (MSKCC), between September 1, 2013 to November 1, 2019. The primary endpoint was to estimate the cumulative incidence of BM in pCR versus non-pCR patients; secondary endpoints included disease free-survival (DFS) and overall survival (OS). After a median follow-up of 3.2 years, 7 out of 286 patients with pCR had a BM while 5 out of 240 non-pCR patients had a BM. The 3-year DFS was significantly higher in the pCR group compared to non-pCR group (95% vs 91 %, p = 0.03) and the same trend was observed for overall survival. In our cohort, despite the better survival outcomes of patients who achieved pCR, we did not observe appreciable differences in the incidence of BM by pCR/non-pCR status. This finding suggests that the BM incidence could not be associated with pCR. Future trials with new small molecules able to cross the blood brain barrier should use more specific biomarkers rather than pCR for patients’ selection.
Semantic systems are mentalistically activated for and by social partners
Authors: Forgács Bálint , Gervain Judit , Parise Eugenio , Gergely György , Elek Lívia Priyanka , Üllei-Kovács Zsuzsanna , Király Ildikó
Published: March 2022

A recently discovered electrophysiological response, the social N400, suggests that we use our language system to track how social partners comprehend language. Listeners show an increased N400 response, when themselves not, only a communicative partner experiences a semantic incongruity. Does the N400 reflect purely semantic or mentalistic computations as well? Do we attribute language comprehension to communicative partners using our semantic systems? In five electrophysiological experiments we identified two subcomponents of the social N400. First, we manipulated the presence-absence of an Observer during object naming: the semantic memory system was activated by the presence of a social partner in addition to semantic predictions for the self. Next, we induced a false belief—and a consequent miscomprehension—in the Observer. Participants showed the social N400, over and above the social presence effect, to labels that were incongruent for the Observer, even though they were congruent for them. This effect appeared only if participants received explicit instructions to track the comprehension of the Observer. These findings suggest that the semantic systems of the brain are not merely sensitive to social information and contribute to the attribution of comprehension, but they appear to be mentalistic in nature.
Fluorescence spectroscopy and multispectral imaging for fingerprinting of aflatoxin-B1 contaminated (Zea mays L.) seeds: a preliminary study
Authors: Bartolić Dragana , Mutavdžić Dragosav , Carstensen Jens Michael , Stanković Slavica , Nikolić Milica , Krstović Saša , Radotić Ksenija
Published: March 2022

Cereal seeds safety may be compromised by the presence of toxic contaminants, such as aflatoxins. Besides being carcinogenic, they have other adverse health effects on humans and animals. In this preliminary study, we used two non-invasive optical techniques, optical fiber fluorescence spectroscopy and multispectral imaging (MSI), for discrimination of maize seeds naturally contaminated with aflatoxin B1 (AFB1) from the uncontaminated seeds. The AFB1-contaminated seeds exhibited a red shift of the emission maximum position compared to the control samples. Using linear discrimination analysis to analyse fluorescence data, classification accuracy of 100% was obtained to discriminate uncontaminated and AFB1-contaminated seeds. The MSI analysis combined with a normalized canonical discriminant analysis, provided spectral and spatial patterns of the analysed seeds. The AFB1-contaminated seeds showed a 7.9 to 9.6-fold increase in the seed reflectance in the VIS region, and 10.4 and 12.2-fold increase in the NIR spectral region, compared with the uncontaminated seeds. Thus the MSI method classified successfully contaminated from uncontaminated seeds with high accuracy. The results may have an impact on development of spectroscopic non-invasive methods for detection of AFs presence in seeds, providing valuable information for the assessment of seed adulteration in the field of food forensics and food safety.
Machine learning-aided design of composite mycotoxin detoxifier material for animal feed
Authors: Lo Dico Giulia , Croubels Siska , Carcelén Verónica , Haranczyk Maciej
Published: March 2022

The development of food and feed additives involves the design of materials with specific properties that enable the desired function while minimizing the adverse effects related with their interference with the concurrent complex biochemistry of the living organisms. Often, the development process is heavily dependent on costly and time-consuming in vitro and in vivo experiments. Herein, we present an approach to design clay-based composite materials for mycotoxin removal from animal feed. The approach can accommodate various material compositions and different toxin molecules. With application of machine learning trained on in vitro results of mycotoxin adsorption–desorption in the gastrointestinal tract, we have searched the space of possible composite material compositions to identify formulations with high removal capacity and gaining insights into their mode of action. An in vivo toxicokinetic study, based on the detection of biomarkers for mycotoxin-exposure in broilers, validated our findings by observing a significant reduction in systemic exposure to the challenging to be removed mycotoxin, i.e., deoxynivalenol (DON), when the optimal detoxifier is administrated to the animals. A mean reduction of 32% in the area under the plasma concentration–time curve of DON-sulphate was seen in the DON + detoxifier group compared to the DON group (P = 0.010).
Angiopathic activity of LRG1 is induced by the IL-6/STAT3 pathway
Authors: Dritsoula Athina , Dowsett Laura , Pilotti Camilla , O’Connor Marie N. , Moss Stephen E. , Greenwood John
Published: March 2022

Leucine-rich α-2-glycoprotein 1 (LRG1) is a secreted glycoprotein that under physiological conditions is produced predominantly by the liver. In disease, its local induction promotes pathogenic neovascularisation while its inhibition leads to reduced dysfunctional angiogenesis. Here we examine the role of interleukin-6 (IL-6) in defective angiogenesis mediated by LRG1. IL-6 treatment induced LRG1 expression in endothelial cells and ex vivo angiogenesis cultures and promoted vascular growth with reduced mural cell coverage. In Lrg1−/− explants, however, IL-6 failed to stimulate angiogenesis and vessels exhibited improved mural cell coverage. IL-6 activated LRG1 transcription through the phosphorylation and binding of STAT3 to a conserved consensus site in the LRG1 promoter, the deletion of which abolished activation. Blocking IL-6 signalling in human lung endothelial cells, using the anti-IL6 receptor antibody Tocilizumab, significantly reduced LRG1 expression. Our data demonstrate that IL-6, through STAT3 phosphorylation, activates LRG1 transcription resulting in vascular destabilisation. This observation is especially timely in light of the potential role of IL-6 in COVID-19 patients with severe pulmonary microvascular complications, where targeting IL-6 has been beneficial. However, our data suggest that a therapy directed towards blocking the downstream angiopathic effector molecule LRG1 may be of greater utility.
Integrative interactomics applied to bovine fescue toxicosis
Authors: Mote Ryan S. , Hill Nicholas S. , Skarlupka Joseph H. , Carpenter Jessica M. , Lourenco Jeferson M. , Callaway Todd R. , Tran ViLinh T. , Liu Ken , Smith Mathew R. , Jones Dean P. , Suen Garret , Filipov Nikolay M.
Published: March 2022

Bovine fescue toxicosis (FT) is caused by grazing ergot alkaloid-producing endophyte (Epichloë coenophiala)-infected tall fescue. Endophyte’s effects on the animal’s microbiota and metabolism were investigated recently, but its effectsin plantaor on the plant–animal interactions have not been considered. We examined multi-compartment microbiota–metabolome perturbations using multi-‘omics (16S and ITS2 sequencing, plus untargeted metabolomics) in Angus steers grazing non-toxic (Max-Q) or toxic (E+) tall fescue for 28 days and in E+ plants. E+ altered the plant/animal microbiota, decreasing most ruminal fungi, with mixed effects on rumen bacteria and fecal microbiota. Metabolic perturbations occurred in all matrices, with some plant-animal overlap (e.g., Vitamin B6 metabolism). Integrative interactomics revealed unique E+ network constituents. Only E+ had ruminal solids OTUs within the network and fecal fungal OTUs in E+ had unique taxa (e.g.,Anaeromyces). Three E+-unique urinary metabolites that could be potential biomarkers of FT and targeted therapeutically were identified.
Clr-f expression regulates kidney immune and metabolic homeostasis
Authors: Zein Haggag S. , Abou-Samra Elias , Scur Michal , Gutsol Alex , Hall Clayton W. , Dasgupta Bishal , Gharibeh Lara , Abujamel Turki , Medina-Luna Daniel , Gamage Gayani S. , Pelino Tessa J. , Nemer Mona , Rahim Mir Munir A. , Steinle Alexander , Parsons Brendon D. , Makrigiannis Andrew P.
Published: March 2022

The C-type lectin-related protein, Clr-f, encoded byClec2hin the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f−/−) by targeted deletions in theClec2hgene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis ofClr-f−/−mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies ofClr-f−/−mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in aRag1−/−Clr-f−/−background reveals thatClr-f−/−mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.
Transplantation of MITO cells, mitochondria activated cardiac progenitor cells, to the ischemic myocardium of mouse enhances the therapeutic effect
Authors: Sasaki Daisuke , Abe Jiro , Takeda Atsuhito , Harashima Hideyoshi , Yamada Yuma
Published: March 2022

Given the potential for myocardial stem cell transplantation as a promising treatment for heart failure, numerous clinical trials have been conducted and its usefulness has been clearly confirmed. However, the low rate of engraftment of transplanted cells has become a clinical problem, and this needs to be improved in the case of transplanting cells to the heart. To address this issue, we report on attempts to prepare mitochondria-activated stem cells (MITO cells) for use in transplantation. MITO cells, which is cardiac progenitor cells (CPCs) activated by the mitochondrial delivery of resveratrol with an anti-oxidant and mitochondrial activation effects were successfully prepared using a mitochondrial targeting nanocarrier (MITO-Porter). The purpose of this study was to validate the therapeutic effect of cell transplantation by the MITO cells using a mouse model of myocardial ischemia–reperfusion. Mouse CPCs were used as transplanted cells. The transplantation of CPCs and MITO cells were conducted after myocardial ischemia–reperfusion, and the therapeutic effect was determined. The MITO cells transplanted group showed increase in postoperative weight gain, improve cardiac function and inhibition of fibrosis compared to the non-transplanted group and the CPC group. The transplantation of MITO cells to the ischemic myocardium showed a stronger transplantation effect compared to conventional CPC transplantation.
Phenotypic disruption of cuticular hydrocarbon production in hybrids between sympatric species of Hawaiian picture-wing Drosophila
Authors: Fezza Thomas J. , Siderhurst Matthew S. , Jang Eric B. , Stacy Elizabeth A. , Price Donald K.
Published: March 2022

Interspecies hybrids can express phenotypic traits far outside the range of parental species. The atypical traits of hybrids provide insight into differences in the factors that regulate the expression of these traits in the parental species. In some cases, the unusual phenotypic traits of hybrids can lead to phenotypic dysfunction with hybrids experiencing reduced survival or reproduction. Cuticular hydrocarbons (CHCs) in insects are important phenotypic traits that serve several functions, including desiccation resistance and pheromones for mating. We used gas chromatography mass spectrometry to investigate the differences in CHC production between two closely related sympatric Hawaiian picture-wing Drosophila species, Drosophila heteroneura and D. silvestris, and their F1 and backcross hybrid offspring. CHC profiles differed between males of the two species, with substantial sexual dimorphism in D. silvestris but limited sexual dimorphism in D. heteroneura. Surprisingly, F1 hybrids did not produce three CHCs, and the abundances of several other CHCs occurred outside the ranges present in the two parental species. Backcross hybrids produced all CHCs with greater variation than observed in F1 or parental species. Overall, these results suggest that the production of CHCs was disrupted in F1 and backcross hybrids, which may have important consequences for their survival or reproduction.
Study on the nonfatigue and fatigue states of orchard workers based on electrocardiogram signal analysis
Authors: Gao Ruitao , Yan Huachao , Duan Jieli , Gao Yu , Cao Can , Li Lanxiao , Guo Liang
Published: March 2022

In recent years, fatigue has become an important issue in modern life that cannot be ignored, especially in some special occupations. Agricultural workers are high-risk occupations that, under fatigue conditions over a long period, will cause health problems. In China, since very few studies have focused on the fatigue state of agricultural workers, we were interested in using electrocardiogram (ECG) signals to analyze the fatigue state of agricultural workers. Healthy agricultural workers were randomly recruited from hilly orchards in South China. Through the field experiment, 130 groups of 5-min interval ECG signals were collected, and we analyzed the ECG signal by HRV. The time domain (meanHR, meanRR, SDNN, RMSSD, SDSD, PNN20, PNN50 and CV), frequency domain (VLF percent, LF percent, HF percent, LF norm, HF norm and LF/HF) and nonlinear parameters (SD1, SD2, SD1/SD2 and sample entropy) were calculated and Spearman correlation coefficient analysis and Mann–Whitney U tests were performed on each parameter for further analysis. For all subjects, nine parameters were slightly correlated in nonfatigue and fatigue state. Six parameters were significantly increased and ten HRV parameters were significantly decreased compared the nonfatigue state. As for males, fifteen parameters were significantly different, and for females, eighteen parameters were significantly different. In addition, the probability density functions of SDNN, SDSD, VLF%, HFnorm and LF/HF were significantly different in nonfatigue and fatigue state for different genders, and the nonlinear parameters become more discrete compared the nonfatigue state. Finally, we obtained the most suitable parameters, which reflect the fatigue characteristics of orchard workers under different genders. The results have instructional significance for identifying fatigue in orchard workers and provide a convincing and valid reference for clinical diagnosis.